Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
  • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
  • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• Developmental disorders include Angelman syndrome, Fragile X syndrome, and Fragile X-associated tremor/ataxia syndrome, Autism Spectrum Disorder, Asperger’s syndrome, Pervasive developmental disorder not otherwise characterized, Childhood Disintegrative Disorder, Williams syndrome, and Jacobsen syndrome. Treatments for these disorders are limited.
• Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the UBE3A gene encoding a ubiquitin E3 ligase. Characteristic features of this disorder include delayed development, intellectual disability, and severe speech impairment. Motor dysfunction is a characteristic feature of Angelman syndrome, e.g., problems with movement and balance (ataxia). M but neither the mechanisms of action nor effective therapeutic strategies have yet been elucidated.
• Fragile X syndrome may be the most common genetic cause of intellectual disability and the most common single-gene cause of autism. It is caused by mutations on the fragile X mental retardation gene (FMR1) and lack of fragile X mental retardation protein, which in turn, leads to decreased inhibition of translation of many synaptic proteins.
• FMR1 fragile X mental retardation gene
• mGluR metabotropic glutamate receptor
• GABA gamma-aminobutyric acid
• the fragile X mouse models show decreased GABA subunit receptors, decreased synthesis of GABA, increased catabolism of GABA, and overall decreased GABAergic input in many regions of the brain.
• Fragile X-associated tremor/ataxia syndrome is a late-onset disorder, usually occurring after age 50. Mutations in the FMR1 gene increase the risk of developing FXTAS. The mutation relates to a DNA segment known as a CGG triplet repeat which is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with FXTAS the CGG segment may be repeated 55 to 200 times. This mutation is known as an FMR1 gene premutation. An expansion of more than 200 repeats, a full mutation, causes Fragile X syndrome discussed above. FXTAS is typically characterized by problems with movement and thinking ability (cognition). FXTAS signs and symptoms usually worsen with age.
• Affected individuals have areas of damage in the cerebellum, the area of the brain that controls movement.
• Characteristic features of FXTAS are intention tremor, which is trembling or shaking of a limb when trying to perform a voluntary movement such as reaching for an object, and problems with coordination and balance (ataxia).
• Many affected individuals develop other movement problems, such as parkinsonism, which includes tremors when not moving (resting tremor), rigidity, and unusually slow movement (bradykinesia).
• affected individuals may have reduced sensation, numbness or tingling, pain, or muscle weakness in the lower limbs, and inability to control the bladder or bowel.
• Other symptoms may include chronic pain syndromes, such as fibromyalgia and chronic migraine, hypothyroidism, hypertension, insomnia, sleep apnea, vertigo, olfactory dysfunction, and hearing loss.
• People with FXTAS commonly have cognitive disabilities such as short-term memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, focusing attention appropriately, and cognitive flexibility.
• Many people with FXTAS experience psychiatric symptoms such as anxiety, depression, moodiness, or irritability.
• symptomatic benefit have been suggested.
• Primidone, beta-blockers such as propanolol, topiramate, carbidopa/levodopa, and benzodiazepines have been suggested to control tremors associated with FXTAS; botulinum toxin for involuntary muscle activities, such as dystonia and spasticity; carbidopa/levodopa, amantadine and buspirone for ataxia; cholinesterase inhibitors such as donepezil, and memantine (an NMDA antagonist) for cognitive deficits and dementia; and antidepressants and antipsychotics for psychiatric symptoms. See, e.g., Hagerman, e/ a/., Clin Interv Aging. 2008 Jun; 3(2): 251-262.
• ASD Autism spectrum disorder
• DSM-5 Diagnostic and Statistical Manual of Mental Disorders
• people with ASD may have: difficulty with communication and interaction with other people, restricted interests and repetitive behaviors, symptoms that hurt the person’s ability to function properly in school, work, and other areas of life.
• Autism is known as a“spectrum” disorder because there is wide variation in the type and severity of symptoms people experience.
• Social communication/interaction behaviors may include: making little or inconsistent eye contact, tending not to look at or listen to people, rarely sharing enjoyment of objects or activities by pointing or showing things to others, failing to, or being slow to, respond to someone calling their name or to other verbal attempts to gain attention, having difficulties with the back and forth of conversation, often talking at length about a favorite subject without noticing that others are not interested or without giving others a chance to respond, having facial expressions, movements, and gestures that do not match what is being said, having an unusual tone of voice that may sound sing-song or flat and robot-like, having trouble understanding another person’s point of view or being unable to predict or understand other people’s actions.
• Restrictive/repetitive behaviors may include: repeating certain behaviors or having unusual behaviors, e.g., repeating words or phrases, a behavior called echolalia, having a lasting intense interest in certain topics, such as numbers, details, or facts, having overly focused interests, such as with moving objects or parts of objects, getting upset by slight changes in a routine, being more or less sensitive than other people to sensory input, such as light, noise, clothing, or temperature, people with ASD may also experience sleep problems and irritability.
• ASD can be a lifelong disorder, treatments and services can improve a person’s symptoms and ability to function.
• AS Asperger’s syndrome
• AS is a developmental disorder classified within ASD, but characterized by a relatively high level of functioning. Individuals with Asperger syndrome exhibit impairment in social interaction and a repetitive, stereotyped pattern of behavior. The individual, however, displays no delay in language or cognitive development, which differentiates Asperger Syndrome from other aspects of autism.
• a distinguishing symptom of AS is a child's obsessive interest in a single object or topic to the exclusion of any other. Children with AS want to know everything about their topic of interest and their
• PDD-NOS Pervasive developmental disorder not otherwise specified
• ASD Pervasive developmental disorder not otherwise specified
• children with PDD-NOS can be characterized as having impaired social interaction, better language skills than children with autism but not as good as those with Asperger's syndrome, fewer repetitive behaviors than children with Asperger's syndrome or autism, and a possible later age of onset.
• Symptoms of PDD-NOS may include behavioral and communication problems such as difficulty using and understanding language, difficulty relating to people, objects, and events, e.g., lack of eye contact, pointing behavior, and lack of facial responses, unusual play with toys and other objects, difficulty with changes in routine or familiar surroundings, repetitive body movements or behavior patterns, such as hand flapping, hair twirling, foot tapping, or more complex movements, inability to cuddle or be comforted, difficulty regulating behaviors and emotions, which may result in temper tantrums, anxiety, and aggression, and emotional breakdowns.
• behavioral and communication problems such as difficulty using and understanding language, difficulty relating to people, objects, and events, e.g., lack of eye contact, pointing behavior, and lack of facial responses, unusual play with toys and other objects, difficulty with changes in routine or familiar surroundings, repetitive body movements or behavior patterns, such as hand flapping, hair twirling, foot tapping, or more complex movements, inability to cuddle or be comforted, difficulty regulating behaviors and emotions, which may result in temper tantrums, anxiety
• CDD Childhood disintegrative disorder
• skills previously acquired are lost almost completely in at least two of the following six functional areas: 1.
• Lack of normal function or impairment also occurs in at least two of the following three areas: 1. social interaction, 2. communication, and 3.
• Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability or learning problems, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems. People with Williams syndrome typically have difficulty with visual-spatial tasks such as drawing and assembling puzzles, but they tend to do well on tasks that involve spoken language, music, and learning by repetition (rote memorization). Affected individuals have outgoing, engaging personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder. Young children with Williams syndrome have distinctive facial features including a broad forehead, a short nose with a broad tip, full cheeks, and a wide mouth with full lips.
• ADD Attention deficit disorder
• Jacobsen syndrome is a developmental disorder caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 1 lq terminal deletion disorder. The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including delays in the development of speech and motor skills (such as sitting, standing, and walking). Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention deficit-hyperactivity disorder (ADHD). Jacobsen syndrome is also associated with an increased likelihood of autism spectrum disorders.
• ADHD attention deficit-hyperactivity disorder
• Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner comer of the eyes (epicanthalfolds), a broad nasal bridge, downturned comers of the mouth, a thin upper lip, and a small lower jaw.
• Jacobsen syndrome Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance.
• Many people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising.
• Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities.
• the disorder can also affect the digestive system, kidneys, and genitalia.
• Methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome are provided.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering to a subject in need thereof an effective amount of (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 -ene- 1 - carboxylic acid or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering to a subject in need thereof an effective amount of (1 S,3 S)- 3 -amino-4-(difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering (lS,3S)-3-amino-4- (difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering (lS,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l- carboxylic acid or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering to a subject in need thereof an effective amount of vigabatrin ((AA)-4-aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof.
• vigabatrin ((AA)-4-aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering vigabatrin ((AA)-4-aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• vigabatrin (AA)-4-aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering vigabatrin ((/t')-4-ami nohex-5 - enoic acid) or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• vigabatrin ((/t')-4-ami nohex-5 - enoic acid) or a pharmaceutically acceptable salt thereof
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering to a subject in need thereof an effective amount of Formula I or a pharmaceutically acceptable salt thereof.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X- associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood
• Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering Formula I or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X- associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering Formula I or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• methods of treating developmental disorders including Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Asperger’s syndrome, Childhood Disintegrative Disorder, Williams Syndrome, and Jacobsen syndrome include administering two or more of: fV)-3-amino-4-
• FIG. l is a bar graph illustrating open field locomotive activity (total distance traveled) of wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl K02 mice administered 0.5% methyl cellulose vehicle, Fmrl K02 mice administered (S)-3-amino-4- (difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.01 mg/kg, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l- ene-l-carboxylic acid 0.1 mg/kg.
• FIG. 2 is a bar graph illustrating open field counter revolutions (CCW) of wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl K02 mice administered 0.5% methyl cellulose, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l- ene-l-carboxylic acid 0.01 mg/kg, Fmrl K02 mice administered (S)-3-amino-4- (difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.1 mg/kg.
• CCW open field counter revolutions
• FIG. 3 is a bar graph illustrating time spent grooming by wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl K02 mice administered 0.5% methyl cellulose, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.01 mg/kg, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.05 mg/kg, and Fmrl K02 mice administered (S)-3- amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.1 mg/kg.
• FIG. 4 is a bar graph illustrating stereotypy count by wild-type mice administered 0 5% methyl cellulose vehicle, Fmrl K02 mice administered 0.5% methyl cellulose, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.01 mg/kg, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.05 mg/kg, and Fmrl K02 mice administered (S)-3- amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.1 mg/kg.
• FIG. 5 is a bar graph illustrating nesting behavior by wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl K02 mice administered 0.5% methyl cellulose, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.01 mg/kg, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.05 mg/kg, and Fmrl K02 mice administered (S)-3- amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.1 mg/kg.
• FIG. 6 is a bar graph latency to eat behavior (novel food in a novel environment) by wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl K02 mice administered 0.5% methyl cellulose, Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l -carboxylic acid 0.01 mg/kg, Fmrl K02 mice administered (S)-3-amino-4- (difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl K02 mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.1 mg/kg.
• FIG. 7 is a bar graph illustrating open field locomotive activity (total distance traveled) of wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl KOI mice administered 0.5% methyl cellulose, Fmrl KOI mice administered (S)-3-amino-4- (difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.01 mg/kg, Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l- ene-l -carboxylic acid 0.1 mg/kg.
• FIG. 8 is a bar graph illustrating open field counter revolutions (CCW) of wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl KOI mice administered 0.5% methyl cellulose, Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l- ene-l -carboxylic acid 0.01 mg/kg, Fmrl KOI mice administered (S)-3-amino-4- (difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.1 mg/kg.
• CCW open field counter revolutions
• FIG. 9 is a bar graph illustrating time spent grooming by wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl KOI mice administered 0.5% methyl cellulose, Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.01 mg/kg, Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl KOI mice administered (S)-3- amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.1 mg/kg.
• FIG. 10 is a bar graph illustrating stereotypy count by wild-type mice administered 0.5% methyl cellulose vehicle, Fmrl KOI mice administered 0.5% methyl cellulose, Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.01 mg/kg, Fmrl KOI mice administered (S)-3-amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.05 mg/kg, and Fmrl KOI mice administered (S)-3- amino-4-(difluoromethylenyl) cyclopent-l-ene-l-carboxylic acid 0.1 mg/kg.
• FIG. 11 is a bar graph illustrating nest building quality by wild-type mice
• methods of treating a developmental disorder include administering (ri)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• methods of treating developmental disorder include administering f V)-3 -a i no-4-( di fl uoro ethyl enyl jcycl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• embodiments include administering to a subject in need thereof an effective amount of (lS,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l-carboxylic acid or a
• developmental disorder include administering (lS,3S)-3-amino-4-
• methods of treating a developmental disorder include
• methods of treating a developmental disorder herein include administering to a subject in need thereof an effective amount of vigabatrin (( RS)-4 - aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof.
• methods of treating a developmental disorder include administering vigabatrin (( RS)-4 - aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• methods of treating a developmental disorder include administering vigabatrin (( RS)-4 - aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• methods and compositions herein involve compounds according to Formula I:
• Ri and R 2 can be independently selected from H, F, Cl, Br and I, where at least one of Ri and R 2 is not H, or a salt of such a compound.
• the stereocenter including an amino substituent can have an ( S) stereochemical configuration.
• methods of treating a developmental disorder include administering to a subject in need thereof an effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof.
• methods of treating a developmental disorder include a compound according to Formula I or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in one or more symptoms of the disorder.
• methods of treating developmental disorder include administering a compound according to Formula I or a pharmaceutically acceptable salt thereof to a subject in need thereof to provide improvement in next day functioning of the subject.
• methods of treating a developmental disorder herein include administering two or more of: (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4- (difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof, and vigabatrin ((AA)-4-aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
• vigabatrin also known as gamma-vinyl-GABA, also known as (RS)- 4-aminohex-5-enoic acid
• RS 4-aminohex-5-enoic acid
• (S)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid may be provided as an acid addition salt, a zwitter ion hydrate, zwitter ion anhydrate, hydrochloride or hydrobromide salt, or in the form of the zwitter ion monohydrate.
• Acid addition salts include but are not limited to, maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bis-methylenesalicylic, methanesulfonic, ethane-di sulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, pantothenic, p-amino-benzoic, glutamic, benzene sulfonic or theophylline acetic acid addition salts, as well as the 8-halotheophyllines, for example 8- bromo-theophylline.
• inorganic acid addition salts including but not limited to, hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric or nitric acid
• (lS,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l-carboxylic acid may be provided as an acid addition salt, a zwitter ion hydrate, zwitter ion anhydrate, hydrochloride or hydrobromide salt, or in the form of the zwitter ion monohydrate.
• Acid addition salts include but are not limited to, maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bis-methylenesalicylic, methanesulfonic, ethane-disulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, pantothenic, p-amino-benzoic, glutamic, benzene sulfonic or theophylline acetic acid addition salts, as well as the 8-halotheophyllines, for example 8- bromo-theophylline.
• inorganic acid addition salts including but not limited to, hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric or nitric acid addition salt
• vigabatrin may be provided as an acid addition salt, a zwitter ion hydrate, zwitter ion anhydrate, hydrochloride or hydrobromide salt, or in the form of the zwitter ion monohydrate.
• Acid addition salts include but are not limited to, maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bis-methylenesalicylic, methanesulfonic, ethane- disulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, pantothenic, p-amino- benzoic, glutamic, benzene sulfonic or theophylline acetic acid addition salts, as well as the 8-halotheophyllines, for example 8-bromo-theophylline.
• inorganic acid addition salts including but not limited to, hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric or nitric acid addition salts
• a compound according to Formula I may be provided as an acid addition salt, a zwitter ion hydrate, zwitter ion anhydrate, hydrochloride or hydrobromide salt, or in the form of the zwitter ion monohydrate.
• Acid addition salts include but are not limited to, maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bis-methylenesalicylic, methanesulfonic, ethane-disulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, pantothenic, p-amino-benzoic, glutamic, benzene sulfonic or theophylline acetic acid addition salts, as well as the 8-halotheophyllines, for example 8-bromo-theophylline.
• inorganic acid addition salts including but not limited to, hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric or nitric acid addition salt
• the developmental disorder is Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Asperger’s syndrome, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Childhood Disintegrative Disorder, Williams Syndrome, or Jacobsen syndrome.
• the developmental disorder is Fragile X syndrome.
• the developmental disorder is Angelman syndrome.
• the developmental disorder is Fragile X-associated tremor/ataxia syndrome (FXTAS).
• the developmental disorder is autism spectrum disorder.
• the developmental disorder is Asperger’s syndrome.
• the developmental disorder is a pervasive developmental disorder not otherwise specified (PDD-NOS).
• the developmental disorder is childhood disintegrative disorder.
• the developmental disorder is Williams syndrome.
• the developmental disorder is Jacobsen syndrome.
• symptoms of Angelman syndrome include delayed development, intellectual disability, cognitive impairment, uncontrolled laughter, excitability, severe speech impairment, hand flapping, and/or motor dysfunction, e.g., problems with movement and balance (ataxia).
• symptoms of Fragile X syndrome include intellectual disability, cognitive impairment, attention disorders, hyperactivity, anxiety, language-processing problems, lack of eye contact, trouble speaking clearly, stuttering, and/or sensitivity to sensory input such as bright light or loud noises.
• symptoms of Fragile X-associated tremor/ataxia syndrome include intention tremor, problems with coordination and balance (ataxia), parkinsonism, reduced sensation, numbness or tingling, pain, or muscle weakness in the lower limbs, inability to control the bladder or bowel, chronic pain syndromes, fibromyalgia, chronic migraine, hypothyroidism, hypertension, insomnia, sleep apnea, vertigo, olfactory dysfunction, hearing loss, cognitive impairment, short-term memory loss, loss of executive function, impulse control, self-monitoring, focusing attention appropriately, cognitive impairment, cognitive flexibility, and/or psychiatric symptoms such as anxiety, depression, moodiness, or irritability.
• symptoms of autism spectrum disorder include difficulty with communication and interaction with other people, restricted interests and repetitive behaviors, making little or inconsistent eye contact, tending not to look at or listen to people, rarely sharing enjoyment of objects or activities by pointing or showing things to others, failing to, or being slow to, respond to someone calling their name or to other verbal attempts to gain attention, having difficulties with the back and forth of conversation, often talking at length about a favorite subject without noticing that others are not interested or without giving others a chance to respond, having facial expressions, movements, and gestures that do not match what is being said, having an unusual tone of voice that may sound sing-song or flat and robot-like, having trouble understanding another person’s point of view or being unable to predict or understand other people’s actions, repeating certain behaviors or having unusual behaviors, e.g., echolalia, having a lasting intense interest in certain topics, such as numbers, details, or facts, having overly focused interests, such as with moving objects or parts of objects, getting upset by slight changes in a routine, being more or less
• symptoms of PDD-NOS include behavioral and communication problems such as difficulty using and understanding language, difficulty relating to people, objects, and events, e.g., lack of eye contact, pointing behavior, and lack of facial responses, unusual play with toys and other objects, difficulty with changes in routine or familiar surroundings, cognitive impairment, repetitive body movements or behavior patterns, such as hand flapping, hair twirling, foot tapping, or more complex movements, inability to cuddle or be comforted, difficulty regulating behaviors and emotions, temper tantrums, anxiety, aggression, and/or emotional breakdowns.
• behavioral and communication problems such as difficulty using and understanding language, difficulty relating to people, objects, and events, e.g., lack of eye contact, pointing behavior, and lack of facial responses, unusual play with toys and other objects, difficulty with changes in routine or familiar surroundings, cognitive impairment, repetitive body movements or behavior patterns, such as hand flapping, hair twirling, foot tapping, or more complex movements, inability to cuddle or be comforted, difficulty regulating behaviors and emotions, temper tantrums, anxiety, aggression, and
• symptoms of childhood disintegrative disorder include, loss of language, motor, social, and other skills previously learned including loss of one or more of:
• CDD subjects may demonstrate autistic symptoms, e.g., cognitive impairment, repetitive behavior and interest patterns, etc.
• symptoms of Williams syndrome include mild to moderate intellectual disability or learning problems, cognitive impairment, unique personality characteristics, distinctive facial features, heart and blood vessel (cardiovascular) problems, difficulty with visual-spatial tasks such as drawing and assembling puzzles, attention deficit disorder (ADD), problems with anxiety and phobias, developmental delays, problems with coordination, and/or short stature.
• symptoms of Jacobsen syndrome include delayed development, including delays in the development of speech and motor skills (such as sitting, standing, and walking), cognitive impairment, learning difficulties, compulsive behavior, short attention span, easy distractibility, attention deficit-hyperactivity disorder (ADHD, autism, and/or feeding difficulties in infancy.
• speech and motor skills such as sitting, standing, and walking
• cognitive impairment such as sitting, standing, and walking
• learning difficulties such as sitting, standing, and walking
• compulsive behavior such as sitting, standing, and walking
• ADHD attention deficit-hyperactivity disorder
• autism autism, and/or feeding difficulties in infancy.
• Cognitive impairment in developmental disorders herein may be measured against normal cognitive function, which refers to the normal physiologic activity of the brain, including, but not limited to, one or more of the following: mental stability, memory/recall abilities, problem solving abilities, reasoning abilities, thinking abilities, judging abilities, ability to discriminate or make choices, capacity for learning, ease of learning, perception, intuition, attention, and awareness, as measured by any criteria suitable in the art.
• Cognitive impairment may also include deficits in mental activities that are mild or that otherwise do not significantly interfere with daily life. Mild cognitive impairment (MCI) is an example of such a condition. A subject with mild cognitive impairment may display symptoms of dementia (e.g., difficulties with language or memory) but the severity of these symptoms is such that a diagnosis of dementia may not be appropriate.
• MCI Mild cognitive impairment
• MMSE MMSE
• NPI Neuropsychiatric Inventory
• CDR Dementia Rating Scale
• CANTAB Cambridge Neuropsychological Test Automated Battery
• SCAG Sandoz Clinical Assessment-Geriatric
• BVRT Benton Visual Retention Test
• MoCA Montreal Cognitive Assessment
• DSST Substitution Test
• Cognitive function may also be measured using imaging techniques such as Positron Emission Tomography (PET), functional magnetic resonance imaging (fMRI), Single Photon Emission Computed Tomography (SPECT), or any other imaging technique that allows one to measure brain function.
• imaging techniques such as Positron Emission Tomography (PET), functional magnetic resonance imaging (fMRI), Single Photon Emission Computed Tomography (SPECT), or any other imaging technique that allows one to measure brain function.
• cognitive function may also be measured with electrophysiological techniques.
• An effective amount of (,S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof is used to respectively treat a subject having Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Asperger’s syndrome, Angelman syndrome, Fragile X syndrome, Fragile X- associated tremor/ataxia syndrome (FXTAS), Childhood Disintegrative Disorder, Williams Syndrome, or Jacobsen syndrome.
• Autism Spectrum Disorder pervasive developmental disorder not otherwise specified, Asperger’s syndrome, Angelman syndrome, Fragile X syndrome, Fragile X- associated tremor/ataxia syndrome (FXTAS), Childhood Disintegrative Disorder, Williams Syndrome, or Jacobsen syndrome.
• An effective amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof is used to respectively treat a subject having Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Asperger’s syndrome, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Childhood Disintegrative Disorder, Williams Syndrome, or Jacobsen syndrome.
• (difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof is used to respectively treat a subject having Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Asperger’s syndrome, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Childhood Disintegrative Disorder, Williams Syndrome, or Jacobsen syndrome.
• An effective amount of vigabatrin ((AA)-4-aminohex-5-enoic acid) or a pharmaceutically acceptable salt thereof is used to respectively treat a subject having Autism Spectrum Disorder, pervasive
• the subject may be an animal, e.g., mammal, e.g., rodents, humans, etc.
• “treat”,“treatment” or“treating” encompass any manner in which symptoms or pathology of a condition, disorder or disease associated with Autism Spectrum Disorder, pervasive developmental disorder not otherwise specified, Asperger’s syndrome, Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Childhood Disintegrative Disorder, Williams Syndrome, or Jacobsen syndrome are ameliorated or otherwise beneficially altered.
• “treat”,“treatment” or “treating” can refer to inhibiting a disease or condition, e.g., arresting or reducing its development or at least one clinical or subclinical symptom thereof.
• “treat”, “treatment” or“treating” can refer to relieving the disease or condition, e.g, causing regression of the disease or condition or at least one of its clinical or subclinical symptoms.
• “treating cognitive impairment” means ameliorating, beneficially altering and/or providing relief from one or more of the symptoms of cognitive impairment.
• the benefit to a subject being treated may be statistically significant, mathematically significant, or at least perceptible to the subject and/or the physician.
• the terms "effective amount” or“therapeutically effective amount” refer to an amount of a compound, material, composition, medicament, or other material that is effective to achieve a particular pharmacological and/or physiologic effect in connection with symptoms of a developmental disorder herein such as, but not limited to, one or more of the following: reducing or eliminating difficulty in sucking, reducing or eliminating difficulty in feeding, reducing or eliminating motor dysfunction, reducing or eliminating poor muscle tone, reducing or eliminating hand flapping, increasing motor skills, increasing coordination, increasing bladder control, reducing or eliminating parkinsonism, reducing or eliminating repetitive body movements, reducing or eliminating intellectual disability, reducing or eliminating learning disability, reducing or eliminating delayed speech development, reducing or eliminating delayed language development, reducing or eliminating language processing problems, reducing or eliminating stuttering, reducing or eliminating loss of executive function, reducing or eliminating cognitive rigidity, reducing or eliminating emotional lability, enhancing impulse control, reducing or eliminating anxiety, reducing or eliminating hyperactivity, reducing or eliminating aggressive behavior, reducing or eliminating or eliminating
• effective amount refers to an amount which may be suitable to prevent a decline in any one or more of the above qualities, or, in embodiments, to improve any one or more of the above qualities, for example, cognitive function or performance, learning rate or ability, problem solving ability, attention span and ability to focus on a task or problem, social behavior, and the like.
• Such effectiveness may be achieved, for example, by administering compositions described herein to an individual or to a population.
• the reduction, or delay of such a decline, or the improvement in an individual or population can be relative to a cohort, e.g., a control subject or a cohort population that has not received the treatment, or been
• the dosage amount can vary according to a variety of factors such as subject-dependent variables (e.g., age, immune system, health, etc.), the disease or disorder being treated, as well as the route of administration and the pharmacokinetics of the agent being administered.
• (difluoromethylidene)cyclopentane-l -carboxylic acid is between about 4 to 6 hours. C max increases in a dose proportional manner over a range of 5 mg - 500 mg; whereas there is a greater than proportional increase in AUCs in the dose range.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid is between 9 and 10 times more potent as an inactivator of GAB A- AT than (lS,3S)-3-amino-4- (difluoromethylidene)cyclopentane-l -carboxylic acid and may exhibit similar
• Vigabatrin ((//k)-4-aminohex-5-enoic acid) is rapidly absorbed, reaching peak concentrations within about 1 to 2.5 hours.
• Administration of a single 37-50 mg/kg dose of an oral solution of vigabatrin results in a tmax of approximately 2.5 hours in neonates and infants, and 1 hour in children.
• Area under plasma concentration-time curves indicated dose- linear pharmacokinetics.
• cerebrospinal concentrations of vigabatrin are 10% of the plasma concentration 6h after a single oral dose.
• the half-life of vigabatrin is between about 5 and 8 hours.
• the terminal half-life of vigabatrin is about 5.7 hours for infants (5 months - 2 years), 9.5 hours for children (10 years - 16 years), and 10.5 hours for adults.
• methods include treating Autism Spectrum Disorder by
• the amount of fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Autism Spectrum Disorder.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Autism Spectrum Disorder may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 1
• dosages may be administered to a subject with Autism Spectrum Disorder once, twice, three or four times daily, every other day, once weekly, or once a month.
• S)-3-amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 - ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day,
• an adult dose for treating Autism Spectrum Disorder can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Autism Spectrum Disorder can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Autism Spectrum Disorder can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 1 hour after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 2 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 3 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 4 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 6 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Autism Spectrum Disorder.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Autism Spectrum Disorder for more than about, e.g ., 2 hours, 4 hours, 6 hours,
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder in combination with one or more of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof (1 S, 3 S)-3-amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Autism Spectrum Disorder in separate dosage forms or combined in one dosage form.
• methods include treating pervasive developmental disorder not otherwise specified (PDD-NOS) by administering to a subject in need thereof about 0.001 mg to about 750 mg of (L')-3 -ami no-4-(difluorom ethyl enyl)cyclopent- l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• PDD-NOS pervasive developmental disorder not otherwise specified
• the amount of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of PDD-NOS.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg,
• compositions for use in treating PDD-NOS may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025
• dosages may be administered to a subject with PDD-NOS once, twice, three or four times daily, every other day, once weekly, or once a month.
• (ri)-3-amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50
• S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7.75 mg
• an adult dose for treating PDD-NOS can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating PDD-NOS can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating PDD-NOS can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 1 hour after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD- NOS for more than 2 hours after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (S)-3 -amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1- carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 3 hours after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 4 hours after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (S)-3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 6 hours after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD- NOS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with PDD-NOS.
• the pharmaceutical compositions may provide improvement in one or more symptoms of PDD-NOS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (S)- 3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having PDD- NOS in combination with one or more of (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having PDD-NOS in separate dosage forms or combined in one dosage form.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl jcycl opent- 1 -ene- 1 - carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4- difluorom ethyl enyl- l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having PDD-NOS simultaneously or at spaced apart intervals.
• methods include treating Asperger’s syndrome by administering to a subject in need thereof about 0.001 mg to about 750 mg of (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of (S)-3 -amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Asperger’s syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Asperger’s syndrome may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.0
• dosages may be administered to a subject with Asperger’s syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• S)-3-amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 - ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day,
• an adult dose for treating Asperger’s syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults.
• an infant or pediatric dose for treating Asperger’s syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses.
• a pediatric dose for treating Asperger’s syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day.
• the subject may be started at a low dose and the dosage is escalated over time.
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject with Asperger’s syndrome via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 1 hour after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 2 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)-3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 3 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 4 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 6 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Asperger’s syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Asperger’s syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Asperger’s syndrome in separate dosage forms or combined in one dosage form.
• (ri)-3-amino-4-(difluorom ethyl enyl)cyclopent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Asperger’s syndrome simultaneously or at spaced apart intervals.
• methods include treating Angelman syndrome by administering to a subject in need thereof about 0.001 mg to about 750 mg of (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Angelman syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Angelman syndrome may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 1
• dosages may be administered to a subject with Angelman syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• (A)-3-ainino-4-(difluoroin ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 - ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day,
• an adult dose for treating Angelman syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Angelman syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Angelman syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• fV)-3 -amino-4-(difluoromethylenyl)cy cl opent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject with Angelman syndrome via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 1 hour after administration to the subject.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 2 hours after administration to the subject.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 3 hours after administration to the subject.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 4 hours after administration to the subject.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 6 hours after administration to the subject.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Angelman syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Angelman syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Angelman syndrome in combination with one or more of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Angelman syndrome in separate dosage forms or combined in one dosage form.
• (L')-3 -ami no-4-(difluorom ethyl enyl)cyclopent- l -ene- 1 - carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Angelman syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X syndrome by administering to a subject in need thereof about 0.005 mg to about 750 mg of (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Fragile X syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Fragile X syndrome may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.0
• dosages may be administered to a subject with Fragile X syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• S)-3-amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 - ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day,
• an adult dose for treating Autism Spectrum Disorder can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults.
• an infant or pediatric dose for treating Fragile X syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses.
• a pediatric dose for treating Fragile X syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day.
• the subject may be started at a low dose and the dosage is escalated over time.
• (S)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject with Fragile X syndrome via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 1 hour after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 2 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 3 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 4 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 6 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Fragile X syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Fragile X syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Fragile X syndrome in combination with one or more of (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Fragile X syndrome in separate dosage forms or combined in one dosage form.
• (S)-3 -amino-4-(difluorom ethyl enyl)cyclopent-l -ene- 1- carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Fragile X syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X-associated tremor/ataxia syndrome (FXTAS) by administering to a subject in need thereof about 0.001 mg to about 750 mg of (X)-3-amino-4-(difluorom ethyl enyl)cyclopent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• FXTAS Fragile X-associated tremor/ataxia syndrome
• the amount of (ri)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of FXTAS.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg,
• compositions for use in treating FXTAS may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to
• dosages may be administered to a subject with FXTAS once, twice, three or four times daily, every other day, once weekly, or once a month.
• (S)- 3- amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50
• S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7.75 mg
• an adult dose for treating FXTAS can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating FXTAS can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating FXTAS can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject with FXTAS via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating FXTAS are provided which include
• composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 1 hour after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 2 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 2 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l
• composition including (S)-3 -amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1- carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 3 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including (A)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 4 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 6 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 6 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l
• compositions including (X)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with FXTAS.
• the pharmaceutical compositions may provide improvement in one or more symptoms of FXTAS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• fV)-3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having FXTAS in combination with one or more of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• (X)-3-amino-4-(difluoromethylenyl)cyclopent-l-ene- l-carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having FXTAS in separate dosage forms or combined in one dosage form.
• (A)-3-amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having FXTAS simultaneously or at spaced apart intervals.
• methods include treating Childhood Disintegrative Disorder (CDD) by administering to a subject in need thereof about 0.005 mg to about 750 mg of (ri)-3-amino- 4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• CDD Childhood Disintegrative Disorder
• the amount of (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of CDD.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating CDD may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175
• dosages may be administered to a subject with CDD once, twice, three or four times daily, every other day, once weekly, or once a month.
• (S)- 3- amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50
• S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7.75 mg
• an adult dose for treating CDD can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating CDD can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating CDD can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 1 hour after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 2 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 3 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 4 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 6 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with CDD. For example, the
• compositions may provide improvement in one or more symptoms of CDD for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (S)- 3 -amino-4-(difluorom ethyl enyljcy cl opent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having CDD in combination with one or more of (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• (ri)-3-amino-4-(difluorom ethyl enyl)cyclopent-l-ene- l-carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having CDD in separate dosage forms or combined in one dosage form.
• ( S )- 3 -amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having CDD simultaneously or at spaced apart intervals.
• methods include treating Williams Syndrome by administering to a subject in need thereof about 0.005 mg to about 750 mg of (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Williams Syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Williams Syndrome may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175
• dosages may be administered to a subject with Williams Syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• S)-3-amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 - ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day,
• an adult dose for treating Williams Syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Williams Syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Williams Syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• fV)-3 -amino-4-(difluoromethylenyl)cy cl opent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject with Williams Syndrome via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Williams Syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 1 hour after administration to the subject.
• methods of treating Williams syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 2 hours after administration to the subject.
• methods of treating Williams syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 3 hours after administration to the subject.
• methods of treating Williams Syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 4 hours after administration to the subject.
• methods of treating Williams Syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 6 hours after administration to the subject.
• methods of treating Williams Syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Williams Syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Williams Syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (S)- 3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having
• Williams Syndrome in combination with one or more of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Williams Syndrome in separate dosage forms or combined in one dosage form.
• (S)-3 -amino-4-(difluorom ethyl enyl)cyclopent-l -ene- 1- carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Williams Syndrome simultaneously or at spaced apart intervals.
• methods include treating Jacobsen syndrome by administering to a subject in need thereof about 0.005 mg to about 750 mg of (ri)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Jacobsen syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Jacobsen syndrome may include (S)-3-amino-4-(difluorom ethyl enyl)cy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to
• dosages may be administered to a subject with Jacobsen syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• S)-3-amino-4-(difluorom ethyl enyl) cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• (S)-3 -a i no-4-( di fl uoro ethyl enyl )cycl opent- 1 - ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day,
• an adult dose for treating Jacobsen syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Jacobsen syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Jacobsen syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• (S)- 3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject with Jacobsen syndrome via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 1 hour after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 2 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 3 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 4 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 6 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Jacobsen syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Jacobsen syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (S)- 3 -amino-4-(difluoromethylenyl)cyclopent- 1 -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Jacobsen syndrome in combination with one or more of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Jacobsen syndrome in separate dosage forms or combined in one dosage form.
• (S)-3 -amino-4-(difluorom ethyl enyljcy cl opent-l -ene- 1- carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Jacobsen syndrome simultaneously or at spaced apart intervals.
• methods include treating Autism Spectrum Disorder by administering to a subject in need thereof about 0.001 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Autism Spectrum Disorder.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg,
• compositions for use in treating Autism Spectrum Disorder may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg,
• 0.01 to 450 mg 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg, 0.025 to 30 mg, 0.025 to 25 mg, 0.025 to 20 mg, 0.025 to 15 mg, 0.025 to 10 mg, 0.025 to 5 mg, 0.025 to lmg, 0.05 to 500 mg, 0.05 to 450 mg, 0.05 to 300
• dosages may be administered to a subject with Autism Spectrum Disorder once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day, 7.75 mg/per day, 7.5 mg/per day, 7.25 mg/per day, 6.0 mg/per day, 5.75 mg/per day, 5.5 mg/per day, 5.25
• an adult dose for treating Autism Spectrum Disorder can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Autism Spectrum Disorder can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Autism Spectrum Disorder can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with Autism Spectrum Disorder via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Autism Spectrum Disorder which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 1 hour after administration to the subject.
• methods of treating Autism Spectrum Disorder are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 2 hours after
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 3 hours after
• Disorder which include administering to a subject in need thereof a
• composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 4 hours after
• Disorder which include administering to a subject in need thereof a
• composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 6 hours after
• Disorder which include administering to a subject in need thereof a
• composition including a compound according to Formula I or a
• compositions wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Autism Spectrum Disorder.
• the pharmaceutical compositions may provide
• Autism Spectrum Disorder for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder in combination with one or more of ( ⁇ S)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid , (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Autism Spectrum Disorder in separate dosage forms or combined in one dosage form.
• A -3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof
• (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Autism Spectrum Disorder in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof (L')-3 -ami no-4-(difluorom ethyl enyl)cyclopent-l -ene- -carboxylic acid or a pharmaceutically acceptable salt thereof, (1 S,3 S)-3-amino-4-difluorom ethyl enyl-l - cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Autism Spectrum Disorder simultaneously or at spaced apart intervals.
• methods include treating pervasive developmental disorder not otherwise specified (PDD-NOS) by administering to a subject in need thereof about 0.001 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of PDD- NOS.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg,
• 0.001 to 700 mg 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg,
• compositions for use in treating PDD-NOS may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg
• 150 to 450 mg 150 to 300 mg, 150 to 250 mg, 150 to 200 mg, 200 to 500 mg, 200 to 450 mg,
• dosages may be administered to a subject with PDD-NOS once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is
• an adult dose for treating PDD-NOS can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating PDD-NOS can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating PDD-NOS can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with PDD-NOS via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes.
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 1 hour after administration to the subject.
• methods of treating PDD-NOS which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 2 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 3 hours after administration to the subject.
• methods of treating PDD-NOS which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 4 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 6 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition a compound according to Formula I or a
• the composition provides improvement in one or more symptoms of PDD-NOS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with PDD-NOS.
• the pharmaceutical compositions may provide improvement in one or more symptoms of PDD- NOS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having PDD-NOS in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having PDD-NOS in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having PDD-NOS simultaneously or at spaced apart intervals.
• methods include treating Asperger’s syndrome by administering to a subject in need thereof about 0.001 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Asperger’s syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Asperger’s syndrome may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg,
• 0.01 to 450 mg 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg, 0.025 to 30 mg, 0.025 to 25 mg, 0.025 to 20 mg, 0.025 to 15 mg, 0.025 to 10 mg, 0.025 to 5 mg, 0.025 to lmg, 0.05 to 500 mg, 0.05 to 450 mg, 0.05 to 300
• dosages may be administered to a subject with Asperger’s syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day, 7.75 mg/per day, 7.5 mg/per day, 7.25 mg/per day, 6.0 mg/per day, 5.75 mg/per day, 5.5 mg/per day, 5.25
• an adult dose for treating Asperger’s syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults.
• an infant or pediatric dose for treating Asperger’s syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses.
• a pediatric dose for treating Asperger’s syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day.
• the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with Asperger’s syndrome via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 1 hour after administration to the subject.
• methods of treating Asperger’s syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Asperger’s syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 3 hours after administration to the subject.
• methods of treating Asperger’s syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Asperger’s syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 6 hours after administration to the subject.
• methods of treating Asperger’s syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• compositions provide improvement of next day functioning of the subject with Asperger’s syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Asperger’s syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having Asperger’s syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I a pharmaceutically acceptable salt thereof , fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, (1 S, 3 S)-3-amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Asperger’s syndrome in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Asperger’s syndrome in separate dosage forms or combined in one dosage form.
• methods include treating Angelman syndrome by administering to a subject in need thereof about 0.001 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Angelman syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Angelman syndrome may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg,
• dosages may be administered to a subject with Angelman syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day, 7.75 mg/per day, 7.5 mg/per day, 7.25 mg/per day, 6.0 mg/per day, 5.75 mg/per day, 5.5 mg/per day, 5.25
• an adult dose for treating Angelman syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Angelman syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Angelman syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with Angelman syndrome via a
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 1 hour after administration to the subject.
• methods of treating Angelman syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Angelman syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 3 hours after administration to the subject.
• methods of treating Angelman syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Angelman syndrome which include administering to a subject in need thereof a pharmaceutical composition including (a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 6 hours after administration to the subject.
• methods of treating Angelman syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• compositions provide improvement of next day functioning of the subject with Angelman syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Angelman syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having Angelman syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof , (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Angelman syndrome in separate dosage forms or combined in one dosage form.
• Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Angelman syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X syndrome by administering to a subject in need thereof about 0.005 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Fragile X syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Fragile X syndrome may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50
• dosages may be administered to a subject with Fragile X syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day, 7.75 mg/per day, 7.5 mg/per day, 7.25 mg/per day, 6.0 mg/per day, 5.75 mg/per day, 5.5 mg/per day, 5.25
• an adult dose for treating Autism Spectrum Disorder can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults.
• an infant or pediatric dose for treating Fragile X syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses.
• a pediatric dose for treating Fragile X syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day.
• the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with Fragile X syndrome via a
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 1 hour after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Fragile X syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 3 hours after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Fragile X syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 6 hours after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of Fragile X syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• compositions provide improvement of next day functioning of the subject with Fragile X syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Fragile X syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having Fragile X syndrome in
• a compound according to Formula I or a pharmaceutically acceptable salt thereof, fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, (1 S, 3 S)-3-amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Fragile X syndrome in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Fragile X syndrome in separate dosage forms or combined in one dosage form.
• methods include treating Fragile X-associated tremor/ataxia syndrome (FXTAS) by administering to a subject in need thereof about 0.001 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• FXTAS Fragile X-associated tremor/ataxia syndrome
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of FXTAS.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• 7.5 to 15 mg, 2.5 to 5 mg with doses of, e.g., about 0.01 mg, 0.025 mg, 0.05 mg, 0.075 mg, 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.75 mg, 0.8 mg, 0.9 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, 4.0 mg, 4.25 mg, 4.5 mg, 4.75 mg, 5 mg, 5.25 mg, 5.5 mg, 5.75 mg, 6 mg, 6.25 mg,
• compositions for use in treating FXTAS may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg,
• 150 to 450 mg 150 to 300 mg, 150 to 250 mg, 150 to 200 mg, 200 to 500 mg, 200 to 450 mg,
• dosages may be administered to a subject with FXTAS once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is
• an adult dose for treating FXTAS can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating FXTAS can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating FXTAS can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with FXTAS via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating FXTAS are provided which include
• methods of treating FXTAS which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 1 hour after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 2 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• composition provides improvement in one or more symptoms of FXTAS for more than 3 hours after administration to the subject.
• methods of treating FXTAS which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 4 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 6 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with FXTAS.
• the pharmaceutical compositions may provide improvement in one or more symptoms of FXTAS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt is administered to a subject having FXTAS in combination with one or more of thereof (L')-3 -ami no-4-(difluorom ethyl enyl)cyclopent- l -ene- 1 -carboxylic acid or a pharmaceutically acceptable salt thereof, (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having FXTAS in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof fV)-3-amino- 4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, (1S, 3 S)-3-amino-4-difluorom ethyl enyl- l-cycl opentanoic acid or a
• pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having FXTAS simultaneously or at spaced apart intervals.
• methods include treating Childhood Disintegrative Disorder (CDD) by administering to a subject in need thereof about 0.005 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• CDD Childhood Disintegrative Disorder
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of CDD.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating CDD may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg, 0.0
• 300 to 400 mg 300 to 350 mg, 350 to 500 mg, 350 to 450 mg, 350 to 400 mg, 400 to 500 mg,
• 400 to 450 mg with 0.001 mg, 0.005 mg, 0.01 mg, 0.025 mg, 0.05 mg, 0.075 mg, 0.1 mg, 0.2 mg, 0.25 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.75 mg, 0.8 mg, 0.9 mg, 1 mg, 1.25 mg, 1.5 mg, 1.75 mg, 2.0 mg, 2.25 mg, 2.5 mg, 2.75 mg, 3.0 mg, 3.25 mg, 3.5 mg, 3.75 mg, 4.0 mg, 4.25 mg, 4.5 mg, 4.75 mg, 5 mg, 5.25 mg, 5.5 mg, 5.75 mg, 6 mg, 6.25 mg, 6.5 mg, 6.75 mg, 7 mg, 7.25 mg, 7.5 mg, 7.75 mg, 8.0 mg, 8.25 mg, 8.5 mg, 8.75 mg, 9.0 mg, 9.25 mg, 9.5 mg, 9.75 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg,
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is
• an adult dose for treating CDD can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating CDD can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating CDD can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with CDD via a pharmaceutical composition.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes.
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 1 hour after administration to the subject.
• methods of treating CDD which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 2 hours after administration to the subject.
• methods of treating CDD are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 3 hours after administration to the subject.
• methods of treating CDD which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 4 hours after administration to the subject.
• methods of treating CDD are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• compositions wherein the composition provides improvement in one or more symptoms of CDD for more than 6 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 8, 10, 12, 14, 16, 18, 20, 22
• compositions provide improvement of next day functioning of the subject with CDD.
• the pharmaceutical compositions may provide improvement in one or more symptoms of CDD for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having CDD in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having CDD in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof fV)-3-amino- 4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, (1S, 3 S)-3-amino-4-difluorom ethyl enyl- l-cycl opentanoic acid or a
• pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having CDD simultaneously or at spaced apart intervals.
• methods include treating Williams Syndrome by administering to a subject in need thereof about 0.005 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Williams Syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Williams Syndrome may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg, 0.0
• dosages may be administered to a subject with Williams Syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day, 7.75 mg/per day, 7.5 mg/per day, 7.25 mg/per day, 6.0 mg/per day, 5.75 mg/per day, 5.5 mg/per day, 5.25
• an adult dose for treating Williams Syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Williams Syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Williams Syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with Williams Syndrome via a
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Williams Syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 1 hour after administration to the subject.
• methods of treating Williams syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Williams syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 3 hours after administration to the subject.
• methods of treating Williams Syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition a compound according to Formula I a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 4 hours after administration to the subject.
• methods of treating Williams Syndrome which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams Syndrome for more than 6 hours after administration to the subject.
• methods of treating Williams Syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• the composition provides improvement in one or more symptoms of Williams Syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Williams Syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Williams Syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having Williams Syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Williams Syndrome in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof, fV)-3 -ami no-4-(difl uorom ethyl enyl jcycl opent-1 -ene-1 -carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Williams Syndrome simultaneously or at spaced apart intervals.
• methods include treating Jacobsen syndrome by administering to a subject in need thereof about 0.005 mg to about 750 mg of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt.
• the amount of a compound according to Formula I or a pharmaceutically acceptable salt thereof, e.g., hydrochloride salt can be between 0.001 and 1000 mg/day, or 0.001 mg/kg/day to 14 mg/kg/day, for treatment of Jacobsen syndrome.
• the daily dosage can be, e.g., in the range of about 0.001 to 750 mg, 0.001 to 700 mg, 0.001 to 500 mg, 0.001 to 250 mg, 0.001 to 200 mg, 0.001 to 175 mg, 0.001 to 150 mg, 0.001 to 125 mg, 0.001 to 100 mg, 0.001 to 75 mg, 0.001 to 50 mg, 0.001 to 30 mg, 0.001 to 25 mg, 0.001 to 20 mg, 0.001 to 15 mg, 0.001 to 10 mg, 0.001 to 5 mg, 0.001 to 4 mg, 0.001 to 3 mg, 0.001 to 2 mg, 0.001 to 1 mg, 0.001 to 0.75 mg, 0.001 to 0.5 mg, 0.001 to 0.25 mg, 0.001 to 0.1 mg, 0.01 to 750 mg, 0.01 to 700 mg, 0.01 to 500 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01
• compositions for use in treating Jacobsen syndrome may include a compound according to Formula I or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.001 to 500 mg, 0.001 to 75 mg, 0.01 to 500 mg, 0.01 to 450 mg, 0.01 to 300 mg, 0.01 to 250 mg, 0.01 to 200 mg, 0.01 to 175 mg, 0.01 to 150 mg, 0.01 to 125 mg, 0.01 to 100 mg, 0.01 to 75 mg, 0.01 to 50 mg, 0.01 to 30 mg, 0.01 to 25 mg, 0.01 to 20 mg, 0.01 to 15 mg, 0.01 to 10 mg, 0.01 to 5 mg, 0.01 to lmg, 0.025 to 500 mg, 0.025 to 450 mg, 0.025 to 300 mg, 0.025 to 250 mg, 0.025 to 200 mg, 0.025 to 175 mg, 0.025 to 150 mg, 0.025 to 125 mg, 0.025 to 100 mg, 0.025 to 75 mg, 0.025 to 50 mg,
• dosages may be administered to a subject with Jacobsen syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 0.01-50 mg/administration.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 11.75 mg/per day, 11.5 mg/per day, 11.25 mg/per day, 11 mg/per day, 10.75 mg/per day, 10.5 mg/per day, 10.25 mg/per day, 10 mg/per day, 9.75 mg/per day, 9.5 mg/per day, 9.25 mg/per day, 9 mg/per day, 8.75 mg/per day, 8.5 mg/per day, 8.25 mg/per day, 7 mg/per day, 7.75 mg/per day, 7.5 mg/per day, 7.25 mg/per day, 6.0 mg/per day, 5.75 mg/per day, 5.5 mg/per day, 5.25
• an adult dose for treating Jacobsen syndrome can be about 0.5 to 50 mg per day or 1 mg to 10 mg per day and can be increased to 75 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Jacobsen syndrome can be from about 0.01 to 10 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Jacobsen syndrome can be 0.075 mg/kg/day to 1.0 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject with Jacobsen syndrome via a
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 1 hour after administration to the subject.
• methods of treating Jacobsen syndrome are provided which include administering to a subject in need thereof a
• composition including a compound according to Formula I or a
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 3 hours after administration to the subject.
• methods of treating include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 3 hours after administration to the subject.
• Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 6 hours after administration to the subject.
• methods of treating include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 6 hours after administration to the subject.
• Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including a compound according to Formula I or a
• the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject with Jacobsen syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Jacobsen syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof is administered to a subject having Jacobsen syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof may be administered to a subject having Jacobsen syndrome in separate dosage forms or combined in one dosage form.
• a compound according to Formula I or a pharmaceutically acceptable salt thereof, fV)-3 -ami no-4-(difl uorom ethyl enyl jcycl opent-1 -ene-1 -carboxylic acid or a pharmaceutically acceptable salt thereof, (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Jacobsen syndrome simultaneously or at spaced apart intervals.
• methods include treating Autism Spectrum Disorder by
• methods include treating Autism Spectrum Disorder by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• the amount of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of Autism Spectrum Disorder.
• the amount of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of Autism Spectrum Disorder.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating Autism Spectrum Disorder may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.01 to 500 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg,
• dosages for treating Autism Spectrum Disorder may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-50 mg/administration.
• (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day, 2 mg/per day, 1 mg/per day, in one or more doses.
• Autism Spectrum Disorder 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/
• an adult dose for treating Autism Spectrum Disorder can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Autism Spectrum Disorder can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Autism Spectrum Disorder can be 0.75 mg/kg/day to 1.5 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 1 hour after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 2 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 3 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 4 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 6 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including
• compositions provide improvement in one or more symptoms of Autism Spectrum Disorder for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• pharmaceutical compositions provide improvement of next day functioning of the subject having Autism Spectrum
• the pharmaceutical compositions may provide improvement in one or more symptoms of Autism Spectrum Disorder for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder in combination with one or more of fV)-3 -a i no-4-( di fl uoro ethyl enyl jcycl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• (lS,3S)-3-amino-4- difluorom ethyl enyl- l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Autism Spectrum Disorder in separate dosage forms or combined in one dosage form.
• (1S, 3 S)-3-amino-4-difluorom ethyl enyl- 1- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Autism Spectrum Disorder simultaneously or at spaced apart intervals.
• methods include treating pervasive developmental disorder not otherwise specified (PDD-NOS) by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (lS,3S)-3-amino-4-difluoromethylenyl-l -cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating PDD-NOS by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• pharmaceutically acceptable salt thereof e.g., a hydrochloride salt thereof
• the amount of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of PDD-NOS.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating PDD-NOS may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.01 to 500 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75
• dosages for treating PDD-NOS may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having PDD-NOS 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3
• an adult dose for treating PDD-NOS can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating PDD-NOS can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating PDD-NOS can be 0.75 mg/kg/day to 1.5 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD- NOS for more than 1 hour after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 2 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD- NOS for more than 4 hours after administration to the subject.
• methods of treating PDD-NOS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 6 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• the composition provides improvement in one or more symptoms of PDD-NOS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject having PDD-NOS.
• the pharmaceutical compositions may provide improvement in one or more symptoms of PDD- NOS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having PDD-NOS in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a
• (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having PDD-NOS simultaneously or at spaced apart intervals.
• methods include treating Asperger’s syndrome by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (l S,3S)-3-amino-4- difluorom ethyl enyl- l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Asperger’s syndrome by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• the amount of (l S,3S)-3-amino- 4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of Asperger’s syndrome. In embodiments, the amount of (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, can be between 0.1 and 1000 mg/day for treatment of Asperger’s syndrome.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating Asperger’s syndrome may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.01 to 500 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to
• dosages for treating Asperger’s syndrome may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Asperger’s syndrome twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-50 mg/administration.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Asperger’s syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day, 2 mg/per day, 1 mg/per day, in one or more doses.
• Asperger’s syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/
• an adult dose for treating Asperger’s syndrome can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Asperger’s syndrome can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Asperger’s syndrome can be 0.75 mg/kg/day to 1.5 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 1 hour after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 2 hours after administration to the subject.
• a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 2 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 3 hours after administration to the subject.
• a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 3 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 4 hours after administration to the subject.
• a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 4 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 6 hours after administration to the subject.
• a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 6 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after
• the pharmaceutical compositions provide improvement of next day functioning of the subject having Asperger’s syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Asperger’s syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Asperger’s syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• 3 -amino-4-(difluorom ethyl enyl)cy cl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Asperger’s syndrome in separate dosage forms or combined in one dosage form.
• (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Asperger’s syndrome simultaneously or at spaced apart intervals.
• methods include treating Angelman syndrome by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Angelman syndrome by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• 4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of Angelman syndrome.
• the amount of (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of Angelman syndrome.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating Angelman syndrome may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• dosages for treating Angelman syndrome may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Angelman syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day
• an adult dose for treating Angelman syndrome can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Angelman syndrome can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Angelman syndrome can be 0.75 mg/kg/day to 1.5 mg/kg/day. In
• the subject may be started at a low dose and the dosage is escalated over time.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating Angelman syndrome.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes.
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• the pharmaceutical compositions provide improvement of next day functioning of the subject having Angelman syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Angelman syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Angelman syndrome in combination with one or more of (ri)-3 -amino-4-(difluorom ethyl enyljcy cl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• 3 -amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Angelman syndrome in separate dosage forms or combined in one dosage form.
• (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof, fV)-3-amino-4- (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Angelman syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X syndrome by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Fragile X syndrome by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• 4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of Fragile X syndrome.
• the amount of (1 S,3 S)- 3 -amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of Fragile X syndrome.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating Fragile X syndrome may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• dosages for treating Fragile X syndrome may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• compositions are administered to a subject having Fragile X syndrome twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-50 mg/administration.
• Fragile X syndrome twice a day e.g., morning and evening
• three times a day e.g., at breakfast, lunch, and dinner
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Fragile X syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day, 2 mg/per day, 1 mg/per day, in one or more doses.
• Fragile X syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/
• an adult dose for treating Fragile X syndrome can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Fragile X syndrome can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Fragile X syndrome can be 0.75 mg/kg/day to 1.5 mg/kg/day. In
• the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 1 hour after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 2 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 3 hours after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 3 hours after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopent
• compositions including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 4 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a
• compositions including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 6 hours after administration to the subject.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a
• compositions including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject having Fragile X syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Fragile X syndrome for more than about, e.g., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Fragile X syndrome in combination with one or more of (ri)-3 -amino-4-(difluorom ethyl enyljcy cl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Fragile X syndrome in separate dosage forms or combined in one dosage form.
• (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having Fragile X syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X-associated tremor/ataxia syndrome (FXTAS) by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• FXTAS Fragile X-associated tremor/ataxia syndrome
• methods include treating FXTAS by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• the amount of (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of FXTAS.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg,
• compositions for use in treating FXTAS may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.01 to 500 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg
• dosages for treating FXTAS may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having FXTAS twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-50 mg/administration.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having FXTAS 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day, 2 mg/per day, 1 mg/per day, in one or more doses.
• FXTAS 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/
• an adult dose for treating FXTAS can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating FXTAS can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating FXTAS can be 0.75 mg/kg/day to 1.5 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating FXTAS.
• Pharmaceutical compositions herein encompass dosage forms.
• Dosage forms herein encompass unit doses.
• various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily.
• Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes.
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating FXTAS are provided which include
• compositions including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 1 hour after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a
• compositions including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 2 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• composition provides improvement in one or more symptoms of FXTAS for more than 3 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 4 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 4 hours after administration to the subject.
• methods of treating FXTAS are provided which include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl eny
• compositions including (lS,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 6 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including (1S, 3 S)-3-amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a
• the composition provides improvement in one or more symptoms of FXTAS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject having FXTAS.
• the pharmaceutical compositions may provide improvement in one or more symptoms of FXTAS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having FXTAS in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a
• (1 S, 3 S)-3-amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having FXTAS simultaneously or at spaced apart intervals.
• methods include treating Childhood Disintegrative Disorder (CDD) by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating CDD by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• 4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of CDD.
• the amount of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of CDD.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating CDD may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.01 to 500 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg,
• dosages for treating CDD may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having CDD twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-50 mg/administration.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having CDD 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day, 2 mg/per day, 1 mg/per day, in one or more doses.
• an adult dose for treating CDD can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating CDD can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating CDD can be 0.75 mg/kg/day to 1.5 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 1 hour after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 2 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 3 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 4 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 6 hours after administration to the subject.
• methods of treating CDD include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of CDD for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject having CDD.
• the pharmaceutical compositions may provide improvement in one or more symptoms of CDD for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having CDD in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l- carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a
• 3 -amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having CDD in separate dosage forms or combined in one dosage form.
• (1 S, 3 S)-3-amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof may be administered to a subject having CDD simultaneously or at spaced apart intervals.
• methods include treating Williams syndrome by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Williams syndrome by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• 4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of Williams syndrome.
• the amount of (1 S,3 S)- 3 -amino-4-difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of Williams syndrome.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating Williams syndrome may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• dosages for treating Williams syndrome may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Williams syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/per day, 2
• an adult dose for treating FXTAS can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults.
• an infant or pediatric dose for treating Williams syndrome can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses.
• a pediatric dose for treating Williams syndrome can be 0.75 mg/kg/day to 1.5 mg/kg/day.
• the subject may be started at a low dose and the dosage is escalated over time.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Williams syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• Williams syndrome for more than 1 hour after administration to the subject.
• methods of treating Williams syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams syndrome for more than 2 hours after administration to the subject.
• methods of treating Williams syndrome include administering to a subject in need thereof a pharmaceutical composition including (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams syndrome for more than 3 hours after administration to the subject.
• methods of treating Williams syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams syndrome for more than 4 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Williams syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions provide improvement of next day functioning of the subject having Williams syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Williams syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Williams syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Williams syndrome simultaneously or at spaced apart intervals.
• methods include treating Jacobsen syndrome by administering to a subject in need thereof about 0.1 mg to about 1500 mg of (l S,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Jacobsen syndrome by administering to a subject in need thereof about 0.5 mg to about 1000 mg of (l S,3S)-3- amino-4-difluoromethylenyl-l-cycl opentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• 4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1500 mg/day, or 0.01 mg/kg/day to 15 mg/kg/day, for treatment of Jacobsen syndrome.
• the amount of (1 S,3 S)- 3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 0.1 and 1000 mg/day for treatment of Jacobsen syndrome.
• the daily dosage can be, e.g., in the range of about 0.1 to 1500 mg, 0.1 to 1250 mg, 0.1 to 1000 mg, 0.1 to 750 mg, 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 1 to 1500 mg, 1 to 1000 mg, 1 to 500 mg, 1 to 300 mg, 1 to 250 mg, 1 to 200 mg, 1 to 175 mg, 1 to 150 mg, 1 to 125 mg, 1 to 100 mg, 1 to 75 mg, 1 to 50 mg, 1 to 30 mg, 1 to 25 mg, 1 to 20 mg, 1 to 15 mg, 0.1 to 10 mg, 1 to 5 mg, 0.1 to l
• compositions for use in treating Jacobsen syndrome may include (l S,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a
• dosages for treating Jacobsen syndrome may be administered to a subject once, twice, three or four times daily, every other day, once weekly, or once a month.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Jacobsen syndrome 100 mg/per day, 95 mg/per day, 90 mg/per day, 85 mg/per day, 80 mg/per day, 75 mg/per day, 70 mg/per day, 65 mg/per day, 60 mg/per day, 55 mg/per day, 50 mg/per day, 45 mg/per day, 40 mg/per day, 35 mg/per day, 30 mg/per day, 25 mg/per day, 20 mg/per day, 15 mg/per day, 10 mg/per day, 5 mg/per day, 4 mg/per day, 3 mg/
• an adult dose for treating Jacobsen syndrome can be about 5 to 80 mg per day and can be increased to 150 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Jacobsen syndrome can be about 0.1 to 50 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Jacobsen syndrome can be 0.75 mg/kg/day to 1.5 mg/kg/day. In
• the subject may be started at a low dose and the dosage is escalated over time.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating Jacobsen syndrome.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily.
• Suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes.
• Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• Jacobsen syndrome for more than 1 hour after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 2 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (l S,3S)-3-amino-4-difluoromethylenyl-l- cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 3 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 4 hours after administration to the subject.
• methods of treating Jacobsen syndrome include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Jacobsen syndrome for more than 6 hours after administration to the subject.
• methods of treating Jacobsen syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including (lS,3S)-3- amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• the pharmaceutical compositions provide improvement of next day functioning of the subject having Jacobsen syndrome.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Jacobsen syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof is administered to a subject having Jacobsen syndrome in combination with one or more of (ri)-3 -amino-4-(difluorom ethyl enyljcy cl opent- l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof.
• (lS,3S)-3-amino-4- difluorom ethyl enyl-l-cy cl opentanoic acid or a pharmaceutically acceptable salt thereof (S)- 3 -amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Jacobsen syndrome in separate dosage forms or combined in one dosage form.
• (lS,3S)-3-amino-4-difluoromethylenyl-l-cyclopentanoic acid or a pharmaceutically acceptable salt thereof fV)-3-amino-4-
• (difluoromethylenyl)cyclopent-l-ene-l-carboxylic acid or a pharmaceutically acceptable salt thereof, or vigabatrin or a pharmaceutically acceptable salt thereof, may be administered to a subject having Jacobsen syndrome simultaneously or at spaced apart intervals.
• methods include treating Autism Spectrum Disorder by
• methods include treating Autism Spectrum Disorder by administering to a subject in need thereof about 100 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 1 and 4000 mg/day, or 0.01 mg/kg/day to 55 mg/kg/day, for treatment of Autism Spectrum Disorder.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, for treatment of Autism Spectrum Disorder can be between 50 and 3000 mg/day, or 0.7 mg/kg/day to 40 mg/kg/day.
• the daily dosage for treatment of Autism Spectrum Disorder can be, e.g., in the range of about 50 to 3000 mg, 50 to 2750 mg, 50 to 2500 mg, 50 to 2225 mg, 50 to 2000 mg, 50 to 1750 mg, 50 to 1500 mg, 50 to 1250 mg, 50 to 1000 mg, 50 to 750 mg, 50 to 500 mg, 50 to 450 mg, 50 to 400 mg, 50 to 350 mg, 50 to 300 mg, 50 to 250 mg, 50 to 200 mg, 50 to 175 mg, 50 to 150 mg, 50 to 125 mg, 50 to 100 mg, 50 to 75 mg, 100 to 3000 mg, 100 to 2750 mg, 100 to 2500 mg, 100 to 2225 mg, 100 to 2000 mg, 100 to 1750 mg, 100 to 1500 mg, 100 to 1250 mg, 100 to 1000 mg, 100 to 750 mg, 100 to 500 mg, 100 to 450 mg, 100 to 400 mg, 100 to 350 mg, 100 to 300 mg, 100 to 250 mg, 100 to 200 mg, 100 to 175 mg, 100 to 150 mg, 100 to 125 mg, 100
• compositions for use in treating Autism Spectrum Disorder may contain vigabatrin or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg, 0.5 to 50 mg, 0.5 to 30 mg, 0.5 to 25 mg, 0.5 to 20 mg, 0.5 to 15 mg, 0.5 to 10
• 300 to 400 mg 300 to 350 mg, 350 to 500 mg, 350 to 450 mg, 350 to 400 mg, 400 to 500 mg,
• 400 to 450 mg with 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, and 500 mg being examples.
• dosages may be administered to a subject having Autism Spectrum
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-500 mg/administration.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Autism Spectrum Disorder 4000 mg/per day, 3000 mg/per day, 2750 mg/per day, 2500 mg/per day, 2250 mg/per day, 2000 mg/per day, 1750 mg/per day, 1500 mg/per day, 1250 mg/per day, 1000 mg/per day, 975 mg/per day, 950 mg/per day, 925 mg/per day, 900 mg/per day, 875 mg/per day, 850 mg/per day, 825 mg/per day, 800 mg/per day, 775 mg/per day, 750 mg/per day, 700 mg/per day, 675 mg/per day, 650 mg/per day, 625 mg/per day, 600 mg/per day, 575 mg/per day, 550 mg/per day, 525 mg/per day, 500 mg/per day, 475 mg/per day, 450 mg/per day, 425 mg/per day, 400 mg/per day, 375 mg/per
• an adult dose for treating Autism Spectrum Disorder can be about 100 to 3000 mg per day and can be increased to 4000 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Autism Spectrum Disorder can be about 10 to 500 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Autism Spectrum Disorder can be 0.7 mg/kg/day to 150 mg/kg/day. In embodiments, the subject may be started at a low dose and the dosage is escalated over time.
• initial daily dosing can be 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily).
• vigabatrin or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating Autism Spectrum Disorder.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Autism Spectrum Disorder which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 1 hour after administration to the subject.
• methods of treating Autism Spectrum Disorder are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 2 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 3 hours after
• Disorder which include administering to a subject in need thereof a
• compositions including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 4 hours after administration to the subject.
• methods of treating Autism Spectrum Disorder include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a
• composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 6 hours after
• Disorder which include administering to a subject in need thereof a
• compositions including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Autism Spectrum Disorder for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions for use in treating Autism Spectrum Disorder provide improvement of next day functioning of the subject.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Autism Spectrum Disorder for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Autism Spectrum Disorder in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a
• vigabatrin or a pharmaceutically acceptable salt thereof (S)- 3- amino-4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, and (lS,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l- carboxylic acid or a pharmaceutically acceptable salt thereof, may be co-administered to a subject having Autism Spectrum Disorder simultaneously or at spaced apart intervals.
• methods include treating pervasive developmental disorder not otherwise specified (PDD-NOS) by administering to a subject in need thereof about 1 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a
• methods include treating PDD-NOS by administering to a subject in need thereof about 100 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 1 and 4000 mg/day, or 0.01 mg/kg/day to 55 mg/kg/day, for treatment of PDD-NOS.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, for treatment of PDD-NOS can be between 50 and 3000 mg/day, or 0.7 mg/kg/day to 40 mg/kg/day.
• the daily dosage for treatment of PDD-NOS can be, e.g., in the range of about 50 to 3000 mg, 50 to 2750 mg, 50 to 2500 mg, 50 to 2225 mg, 50 to 2000 mg, 50 to 1750 mg, 50 to 1500 mg, 50 to 1250 mg, 50 to 1000 mg, 50 to 750 mg, 50 to 500 mg, 50 to 450 mg, 50 to 400 mg, 50 to 350 mg, 50 to 300 mg, 50 to 250 mg, 50 to 200 mg, 50 to 175 mg, 50 to 150 mg, 50 to 125 mg,
• compositions for use in treating PDD-NOS may contain vigabatrin or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg, 0.5 to 50 mg, 0.5 to 30 mg, 0.5 to 25 mg, 0.5 to 20 mg, 0.5 to 15 mg, 0.5 to 15 mg, 0.5 to 150
• dosages may be administered to a subject having PDD-NOS once, twice, three or four times daily, every other day, once weekly, or once a month.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having PDD-NOS twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-500 mg/administration.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having PDD-NOS 4000 mg/per day, 3000 mg/per day, 2750 mg/per day, 2500 mg/per day, 2250 mg/per day, 2000 mg/per day, 1750 mg/per day, 1500 mg/per day, 1250 mg/per day, 1000 mg/per day, 975 mg/per day, 950 mg/per day, 925 mg/per day, 900 mg/per day, 875 mg/per day, 850 mg/per day, 825 mg/per day, 800 mg/per day, 775 mg/per day, 750 mg/per day, 700 mg/per day, 675 mg/per day, 650 mg/per day, 625 mg/per day, 600 mg/per day, 575 mg/per day, 550 mg/per day, 525 mg/per day, 500 mg/per day, 475 mg/per day, 450 mg/per day, 425 mg/per day, 400 mg/per day, 375 mg
• an adult dose for treating PDD-NOS can be about 100 to 3000 mg per day and can be increased to 4000 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating PDD-NOS can be about 10 to 500 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating PDD-NOS can be 0.7 mg/kg/day to 150 mg/kg/day. In embodiments, the subject having PDD-NOS may be started at a low dose and the dosage is escalated over time.
• initial daily dosing can be 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily).
• vigabatrin or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating PDD-NOS.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating PDD-NOS which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 1 hour after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 2 hours after administration to the subject.
• methods of treating PDD-NOS which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 3 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 4 hours after administration to the subject.
• methods of treating PDD-NOS which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 6 hours after administration to the subject.
• methods of treating PDD-NOS are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of PDD-NOS for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions for use in treating PDD-NOS provide improvement of next day functioning of the subject.
• the pharmaceutical compositions may provide improvement in one or more symptoms of PDD-NOS for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having PDD-NOS in combination with one or more of fV)-3-amino- 4-(difluoromethylenyl)cyclopent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or (l S,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having PDD-NOS in separate dosage forms or combined in one dosage form.
• vigabatrin or a pharmaceutically acceptable salt thereof (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, and (l S,3S)-3-amino-4-
• (difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof may be co-administered to a subject having PDD-NOS simultaneously or at spaced apart intervals.
• methods include treating Asperger’s syndrome by administering to a subject in need thereof about 1 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Asperger’s syndrome by administering to a subject in need thereof about 100 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 1 and 4000 mg/day, or 0.01 mg/kg/day to 55 mg/kg/day, for treatment of Asperger’s syndrome. In embodiments, the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, for treatment of Asperger’s syndrome can be between 50 and 3000 mg/day, or 0.7 mg/kg/day to 40 mg/kg/day.
• the daily dosage for treatment of Asperger’s syndrome can be, e.g., in the range of about 50 to 3000 mg, 50 to 2750 mg, 50 to 2500 mg, 50 to 2225 mg, 50 to 2000 mg, 50 to 1750 mg, 50 to 1500 mg, 50 to 1250 mg, 50 to 1000 mg, 50 to 750 mg, 50 to 500 mg, 50 to 450 mg, 50 to 400 mg, 50 to 350 mg, 50 to 300 mg, 50 to 250 mg, 50 to 200 mg, 50 to 175 mg, 50 to 150 mg, 50 to 125 mg, 50 to 100 mg, 50 to 75 mg, 100 to 3000 mg, 100 to 2750 mg, 100 to 2500 mg, 100 to 2225 mg, 100 to 2000 mg, 100 to 1750 mg, 100 to 1500 mg, 100 to 1250 mg, 100 to 1000 mg, 100 to 750 mg, 100 to 500 mg, 100 to 450 mg, 100 to 400 mg, 100 to 350 mg, 100 to 300 mg, 100 to 250 mg, 100 to 200 mg, 100 to 175 mg, 100 to 150 mg, 100 to 450
• compositions for use in treating Asperger’s syndrome may contain vigabatrin or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg, 0.5 to 50 mg, 0.5 to 30 mg, 0.5 to 25 mg, 0.5 to 20 mg, 0.5 to 15 mg, 0.5 to 15 mg, 0.5 to
• 300 to 400 mg 300 to 350 mg, 350 to 500 mg, 350 to 450 mg, 350 to 400 mg, 400 to 500 mg,
• 400 to 450 mg with 0.1 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 17.5 mg, 20 mg, 22.5 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, and 500 mg being examples.
• dosages may be administered to a subject having Asperger’s syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Asperger’s syndrome twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-500 mg/administration.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Asperger’s syndrome 4000 mg/per day, 3000 mg/per day, 2750 mg/per day, 2500 mg/per day, 2250 mg/per day, 2000 mg/per day, 1750 mg/per day, 1500 mg/per day, 1250 mg/per day, 1000 mg/per day, 975 mg/per day, 950 mg/per day, 925 mg/per day, 900 mg/per day, 875 mg/per day, 850 mg/per day, 825 mg/per day, 800 mg/per day, 775 mg/per day, 750 mg/per day, 700 mg/per day, 675 mg/per day, 650 mg/per day, 625 mg/per day, 600 mg/per day, 575 mg/per day, 550 mg/per day, 525 mg/per day, 500 mg/per day, 475 mg/per day, 450 mg/per day, 425 mg/per day, 400 mg/per day, 375
• an adult dose for treating Asperger’s syndrome can be about 100 to 3000 mg per day and can be increased to 4000 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Asperger’s syndrome can be about 10 to 500 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Asperger’s syndrome can be 0.7 mg/kg/day to 150 mg/kg/day. In embodiments, the subject having Asperger’s syndrome may be started at a low dose and the dosage is escalated over time.
• initial daily dosing can be 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily).
• vigabatrin or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating Asperger’s syndrome.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 1 hour after administration to the subject.
• methods of treating Asperger’s syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 2 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 3 hours after administration to the subject.
• methods of treating Asperger’s syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 4 hours after administration to the subject.
• methods of treating Asperger’s syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 6 hours after administration to the subject.
• methods of treating Asperger’s syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Asperger’s syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the pharmaceutical compositions for use in treating Asperger’s syndrome provide improvement of next day functioning of the subject.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Asperger’s syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Asperger’s syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or (l S,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l- carboxylic acid or a pharmaceutically acceptable salt thereof.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Asperger’s syndrome in separate dosage forms or combined in one dosage form.
• vigabatrin or a pharmaceutically acceptable salt thereof (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, and (l S,3S)-3-amino-4- (difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof, may be co-administered to a subject having Asperger’s syndrome simultaneously or at spaced apart intervals.
• methods include treating Angelman syndrome by administering to a subject in need thereof about 1 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof. In embodiments, methods include treating Angelman syndrome by administering to a subject in need thereof about 100 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 1 and 4000 mg/day, or 0.01 mg/kg/day to 55 mg/kg/day, for treatment of Angelman syndrome.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, for treatment of Angelman syndrome can be between 50 and 3000 mg/day, or 0.7 mg/kg/day to 40 mg/kg/day.
• the daily dosage for treatment of Angelman syndrome can be, e.g., in the range of about 50 to 3000 mg, 50 to 2750 mg, 50 to 2500 mg,
• compositions for use in treating Angelman syndrome may contain vigabatrin or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg,
• dosages may be administered to a subject having Angelman syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Angelman syndrome twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-500 mg/administration.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Angelman syndrome 4000 mg/per day, 3000 mg/per day, 2750 mg/per day, 2500 mg/per day, 2250 mg/per day, 2000 mg/per day, 1750 mg/per day, 1500 mg/per day, 1250 mg/per day, 1000 mg/per day, 975 mg/per day, 950 mg/per day, 925 mg/per day, 900 mg/per day, 875 mg/per day, 850 mg/per day, 825 mg/per day, 800 mg/per day, 775 mg/per day, 750 mg/per day, 700 mg/per day, 675 mg/per day, 650 mg/per day, 625 mg/per day, 600 mg/per day, 575 mg/per day, 550 mg/per day, 525 mg/per day, 500 mg/per day, 475 mg/per day, 450 mg/per day, 425 mg/per day, 400 mg/per day, 375 mg/per day,
• an adult dose for treating Angelman syndrome can be about 100 to 3000 mg per day and can be increased to 4000 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Angelman syndrome can be about 10 to 500 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating Angelman syndrome can be 0.7 mg/kg/day to 150 mg/kg/day. In embodiments, the subject having Angelman syndrome may be started at a low dose and the dosage is escalated over time.
• initial daily dosing can be 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily).
• vigabatrin or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating Angelman syndrome.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 1 hour after administration to the subject.
• methods of treating Angelman syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 2 hours after administration to the subject.
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 3 hours after administration to the subject.
• methods of treating Angelman syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of
• methods of treating Angelman syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 6 hours after administration to the subject.
• methods of treating Angelman syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• the composition provides improvement in one or more symptoms of Angelman syndrome for more than 8, 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration to the subject.
• compositions for use in treating Angelman syndrome provide improvement of next day functioning of the subject.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Angelman syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Angelman syndrome in combination with one or more of (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or (l S,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l- carboxylic acid or a pharmaceutically acceptable salt thereof.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Angelman syndrome in separate dosage forms or combined in one dosage form.
• vigabatrin or a pharmaceutically acceptable salt thereof (ri)-3-amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, and (l S,3S)-3-amino-4- (difluoromethylidene)cyclopentane-l -carboxylic acid or a pharmaceutically acceptable salt thereof, may be co-administered to a subject having Angelman syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X syndrome by administering to a subject in need thereof about 1 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating Fragile X syndrome by administering to a subject in need thereof about 100 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 1 and 4000 mg/day, or 0.01 mg/kg/day to 55 mg/kg/day, for treatment of Fragile X syndrome.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, for treatment of Fragile X syndrome can be between 50 and 3000 mg/day, or 0.7 mg/kg/day to 40 mg/kg/day.
• the daily dosage for treatment of Fragile X syndrome can be, e.g., in the range of about 50 to 3000 mg, 50 to 2750 mg, 50 to 2500 mg,
• compositions for use in treating Fragile X syndrome may contain vigabatrin or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg,
• dosages may be administered to a subject having Fragile X syndrome once, twice, three or four times daily, every other day, once weekly, or once a month.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Fragile X syndrome twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-500 mg/administration.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having Fragile X syndrome 4000 mg/per day, 3000 mg/per day, 2750 mg/per day, 2500 mg/per day, 2250 mg/per day, 2000 mg/per day, 1750 mg/per day, 1500 mg/per day, 1250 mg/per day, 1000 mg/per day, 975 mg/per day, 950 mg/per day, 925 mg/per day, 900 mg/per day, 875 mg/per day, 850 mg/per day, 825 mg/per day, 800 mg/per day, 775 mg/per day, 750 mg/per day, 700 mg/per day, 675 mg/per day, 650 mg/per day, 625 mg/per day, 600 mg/per day, 575 mg/per day, 550 mg/per day, 525 mg/per day, 500 mg/per day, 475 mg/per day, 450 mg/per day, 425 mg/per day, 400 mg/per day, 375
• an adult dose for treating Fragile X syndrome can be about 100 to 3000 mg per day and can be increased to 4000 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating Fragile X syndrome can be about 10 to 500 mg per day once or in 2, 3 or 4 divided doses. In
• a pediatric dose for treating Fragile X syndrome can be 0.7 mg/kg/day to 150 mg/kg/day.
• the subject having Fragile X syndrome may be started at a low dose and the dosage is escalated over time.
• initial daily dosing can be 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily).
• vigabatrin or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating Fragile X syndrome.
• compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating Fragile X syndrome include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 1 hour after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 2 hours after administration to the subject.
• methods of treating Fragile X syndrome which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 3 hours after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 4 hours after administration to the subject.
• methods of treating Fragile X syndrome which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 6 hours after administration to the subject.
• methods of treating Fragile X syndrome are provided which include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of Fragile X syndrome for more than 8, 10, 12, 14,
• compositions for use in treating Fragile X syndrome provide improvement of next day functioning of the subject.
• the pharmaceutical compositions may provide improvement in one or more symptoms of Fragile X syndrome for more than about, e.g ., 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours or 24 hours after administration and waking from a night of sleep.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Fragile X syndrome in combination with one or more of ( S )- 3 -amino-4-(difluorom ethyl enyljcy cl opent-l-ene-l -carboxylic acid or a pharmaceutically acceptable salt thereof, or (lS,3S)-3-amino-4-(difluoromethylidene)cyclopentane-l- carboxylic acid or a pharmaceutically acceptable salt thereof.
• vigabatrin or a pharmaceutically acceptable salt thereof may be administered to a subject having Fragile X syndrome in separate dosage forms or combined in one dosage form.
• vigabatrin or a pharmaceutically acceptable salt thereof may be co-administered to a subject having Fragile X syndrome simultaneously or at spaced apart intervals.
• methods include treating Fragile X-associated tremor/ataxia syndrome (FXTAS) by administering to a subject in need thereof about 1 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• methods include treating FXTAS by administering to a subject in need thereof about 100 mg to about 4000 mg of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof.
• the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof can be between 1 and 4000 mg/day, or 0.01 mg/kg/day to 55 mg/kg/day, for treatment of FXTAS. In embodiments, the amount of vigabatrin or a pharmaceutically acceptable salt thereof, e.g., a hydrochloride salt thereof, for treatment of FXTAS can be between 50 and 3000 mg/day, or 0.7 mg/kg/day to 40 mg/kg/day.
• the daily dosage for treatment of FXTAS can be, e.g., in the range of about 50 to 3000 mg, 50 to 2750 mg, 50 to 2500 mg, 50 to 2225 mg, 50 to 2000 mg, 50 to 1750 mg, 50 to 1500 mg, 50 to 1250 mg, 50 to 1000 mg, 50 to 750 mg, 50 to 500 mg, 50 to 450 mg, 50 to 400 mg, 50 to 350 mg, 50 to 300 mg, 50 to 250 mg, 50 to 200 mg, 50 to 175 mg, 50 to 150 mg, 50 to 125 mg, 50 to 100 mg, 50 to 75 mg, 100 to 3000 mg, 100 to 2750 mg, 100 to 2500 mg, 100 to 2225 mg, 100 to 2000 mg, 100 to 1750 mg, 100 to 1500 mg, 100 to 1250 mg, 100 to 1000 mg, 100 to 750 mg, 100 to 500 mg, 100 to 450 mg, 100 to 400 mg, 100 to 350 mg, 100 to 300 mg, 100 to 250 mg, 100 to 200 mg, 100 to 175 mg, 100 to 150 mg, 100 to 125 mg,
• compositions for use in treating FXTAS may contain vigabatrin or a pharmaceutically acceptable salt thereof in an amount of, e.g., about 0.1 to 500 mg, 0.1 to 450 mg, 0.1 to 300 mg, 0.1 to 250 mg, 0.1 to 200 mg, 0.1 to 175 mg, 0.1 to 150 mg, 0.1 to 125 mg, 0.1 to 100 mg, 0.1 to 75 mg, 0.1 to 50 mg, 0.1 to 30 mg, 0.1 to 25 mg, 0.1 to 20 mg, 0.1 to 15 mg, 0.1 to 10 mg, 0.1 to 5 mg, 0.1 to lmg, 0.5 to 500 mg, 0.5 to 450 mg, 0.5 to 300 mg, 0.5 to 250 mg, 0.5 to 200 mg, 0.5 to 175 mg, 0.5 to 150 mg, 0.5 to 125 mg, 0.5 to 100 mg, 0.5 to 75 mg, 0.5 to 50 mg, 0.5 to 30 mg, 0.5 to 25 mg, 0.5 to 20 mg, 0.5 to 15 mg, 0.5 to 15 mg, 0.5 to 150 mg
• dosages may be administered to a subject having FXTAS once, twice, three or four times daily, every other day, once weekly, or once a month.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having FXTAS twice a day, (e.g., morning and evening), or three times a day (e.g., at breakfast, lunch, and dinner), at a dose of 1-500 mg/administration.
• vigabatrin or a pharmaceutically acceptable salt thereof is administered to a subject having FXTAS 4000 mg/per day, 3000 mg/per day, 2750 mg/per day, 2500 mg/per day, 2250 mg/per day, 2000 mg/per day, 1750 mg/per day, 1500 mg/per day, 1250 mg/per day, 1000 mg/per day, 975 mg/per day, 950 mg/per day, 925 mg/per day, 900 mg/per day, 875 mg/per day, 850 mg/per day, 825 mg/per day, 800 mg/per day, 775 mg/per day, 750 mg/per day, 700 mg/per day, 675 mg/per day, 650 mg/per day, 625 mg/per day, 600 mg/per day, 575 mg/per day, 550 mg/per day, 525 mg/per day, 500 mg/per day, 475 mg/per day, 450 mg/per day, 425 mg/per day, 400 mg/per day, 375 mg/
• an adult dose for treating FXTAS can be about 100 to 3000 mg per day and can be increased to 4000 mg per day. Dosages can be lower for infants and children than for adults. In embodiments, an infant or pediatric dose for treating FXTAS can be about 10 to 500 mg per day once or in 2, 3 or 4 divided doses. In embodiments, a pediatric dose for treating FXTAS can be 0.7 mg/kg/day to 150 mg/kg/day. In embodiments, the subject having FXTAS may be started at a low dose and the dosage is escalated over time.
• initial daily dosing can be 50 mg/kg/day given in two divided doses (25 mg/kg twice daily); subsequent dosing can be titrated by 25 mg/kg/day to 50 mg/kg/day increments every 3 days, up to a maximum of 150 mg/kg/day given in 2 divided doses (75 mg/kg twice daily).
• vigabatrin or a pharmaceutically acceptable salt thereof is administered via a pharmaceutical composition for use in treating FXTAS.
• Pharmaceutical compositions herein encompass dosage forms. Dosage forms herein encompass unit doses. In embodiments, as discussed below, various dosage forms including conventional formulations and modified release formulations can be administered one or more times daily. Any suitable route of administration may be utilized, e.g., oral, rectal, nasal, pulmonary, vaginal, sublingual, transdermal, intravenous, intraarterial, intramuscular, intraperitoneal and subcutaneous routes. Suitable dosage forms include tablets, capsules, oral liquids, powders, aerosols, transdermal modalities such as topical liquids, patches, creams and ointments, parenteral formulations and suppositories.
• methods of treating FXTAS are provided which include
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a pharmaceutically acceptable salt thereof wherein the composition provides improvement in one or more symptoms of FXTAS for more than 2 hours after administration to the subject.
• methods of treating FXTAS include administering to a subject in need thereof a pharmaceutical composition including vigabatrin or a

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