WO2021194796A1 - Méthode de traitement de troubles neurologiques à l'aide d'un entraînement de voie synaptique - Google Patents

Méthode de traitement de troubles neurologiques à l'aide d'un entraînement de voie synaptique Download PDF

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WO2021194796A1
WO2021194796A1 PCT/US2021/022517 US2021022517W WO2021194796A1 WO 2021194796 A1 WO2021194796 A1 WO 2021194796A1 US 2021022517 W US2021022517 W US 2021022517W WO 2021194796 A1 WO2021194796 A1 WO 2021194796A1
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synaptic
pathway
brain
depression
treatment
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PCT/US2021/022517
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English (en)
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Joseph Rustick
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Joseph Rustick
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Priority claimed from US16/827,546 external-priority patent/US20200222656A1/en
Application filed by Joseph Rustick filed Critical Joseph Rustick
Priority to IL296693A priority Critical patent/IL296693A/en
Priority to CA3172981A priority patent/CA3172981A1/fr
Priority to MX2022011862A priority patent/MX2022011862A/es
Priority to BR112022019234A priority patent/BR112022019234A2/pt
Priority to EP21776197.2A priority patent/EP4126199A4/fr
Publication of WO2021194796A1 publication Critical patent/WO2021194796A1/fr
Priority to ZA2022/10356A priority patent/ZA202210356B/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36021—External stimulators, e.g. with patch electrodes for treatment of pain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • This invention relates to methods for the treatment of a neurologic condition.
  • the invention relates to methods of treating depression, bipolar disorder, mania, alcoholism and post-traumatic stress disorder by training synaptic pathways in the brain and affecting the hippocampus by changing its structure.
  • Persons suffering from depression or bipolar disorder may experience a constellation of debilitating symptoms, including a lack of interest and pleasure in daily activities, significant weight loss or gain, insomnia or excessive sleeping, lack of energy, inability to concentrate, feelings of worthlessness, helplessness, excessive guilt, and recurrent thoughts of death or suicide. Depression can occur as a primary mental health disorder or may arise secondary to an unrelated primary illness. Similarly, alcohol abuse has significant negative physical, social and emotional effects.
  • CBT cognitive behavioral therapy
  • ECT electroconvulsive therapy
  • CBT is effective in many cases, particularly when symptoms are mild to moderate and of recent onset, but less so in chronic or severe depression.
  • CBT has been shown to be more effective with combined with medications, and vise-versa.
  • Treatment of depression with medications is generally safe, however, onset of a therapeutic effect is gradual and may take at least several weeks to manifest, with maximal improvement seen only after eight weeks. If medications are discontinued, the symptoms generally return, often necessitating lifetime pharmacologic therapy.
  • medications alone are effective in only forty to sixty percent (40% - 60%) of cases, combined CBT and medications are only effective in sixty to seventy percent (60% - 70%) of cases.
  • ECT is useful in up to ninety percent (90%) of patients and immediately effective, however, ECT does cause a level of brain damage and is associated with significant side effects, including effects on memory and cognitive impairment. Only about twenty percent (20%) of those with depression receive any treatment, and a significant percentage of those who are treated do not achieve significant or lasting improvement.
  • Available treatments for alcohol abuse include programs such as Alcoholics Anonymous and application often of a twelve-step program and a buddy system to resist the urge to imbibe. Such treatments if they work are quoted as effective in thirteen percent (13%) at five years. It deals with resisting the urge but does not reprogram the individual so they no longer desire alcohol.
  • Embodiments of the present invention include methods for treatment of a neurologic condition by synaptic training and treatments effecting the structure of the hippocampus to lessen or eliminate the compulsion to consume alcohol.
  • a method of treating a neurologic condition by synaptic pathway training comprising steps of activating a synaptic pathway with a pharmacologic agent; and stimulating the activated synaptic pathway.
  • some of the embodiments of the subject invention combines the application of a preselected drug therapy with a non-drug stimulus therapy to enhance and prolong the drug therapy effect.
  • the pharmacologic agent comprises an N-methyl-D-aspartate receptor antagonist. In some embodiments, the pharmacologic agent comprises ketamine. In some embodiments, the pharmacologic agent is a member selected from the group of pharmacologic agents consisting of scopolamine, Namenda, dextromethorphan, amantadine, dextropropoxyphene, and ketobemidone.
  • the pharmacologic agent is psilocybin. In some embodiments, the pharmacologic agent is phencyclidine. In some embodiments, the pharmacologic agent is lysergic acid diethylamide. There may be other embodiments, pharmacologic agents which produce additional synaptic connections in specific areas of the brain. These embodiments will treat other conditions reflecting disease processes of specific areas of the brain effected.
  • the neurologic condition is depression. In some embodiments, the neurologic condition is bipolar disorder. In some embodiments, the neurologic condition is post-traumatic stress disorder. In some embodiments the condition is alcoholism and possibly other conditions which negatively alter and impact the size and/or functioning of the hippocampus or other areas
  • stimulating the synaptic pathway comprises performance of a cognitive training exercise.
  • the stimulating step comprises exposure of a person to a sensory stimulus.
  • the stimulating step comprises applying a magnetic field to a region of a brain.
  • the stimulating step comprises applying a potential voltage difference to a region of a brain.
  • the stimulating step comprises providing an auditory stimulus.
  • the stimulating step comprises providing a visible-wavelength light stimulus.
  • the initial step is the application of a pharmacological agent followed by a regimen of non- pharmacological cognitive stimuli.
  • a method of enhancing treatment of a neurologic condition comprising steps treating the condition with a pharmacologic agent to alter the synaptic pathways; and extending a treatment result by repeatedly activating the synaptic pathway with a neural stimulating means.
  • activating the synaptic pathway comprises performance of a cognitive training exercise. In some embodiments, activating the synaptic pathway comprises providing an external source of stimulation. In some embodiments, the external source is a magnetic field, a potential voltage difference, an auditory stimulus or a combination of stimuli.
  • a method of treating a neurologic condition or alcoholism by synaptic pathway training comprising steps activating a synaptic pathway by administering at least one dose of ketamine, at least 0.5 mg/kg; and stimulating the activated synaptic pathway by performing a cognitive exercise for at least thirty (30) minutes daily.
  • the neurologic condition is bipolar disorder, depression, mania, or post-traumatic stress disorder.
  • FIG. 1 is a flowchart showing steps of a method for treating alcoholism or a neurologic condition using synaptic pathway training
  • FIG. 2 is a flowchart showing steps of an additional method for treating alcoholism or a neurological condition using synaptic pathway training
  • FIG. 3 is a flowchart showing steps of another method for treating alcoholism or a neuroglial condition using synaptic pathway training.
  • FIG. 4 is a flowchart showing more detailed steps of another method of treatment for alcoholism or other neurological condition.
  • the disclosed invention relates to methods for the treatment of alcoholism or a neurologic condition.
  • the invention relates to methods of treating alcoholism, bipolar disorder, depression, mania, post-traumatic stress disorder, and other neurologic conditions by training synaptic pathways in the brain.
  • “Synaptic density” means the number of synapses per unit volume of neural tissue, including brain tissue.
  • “Synaptic pathway” is used to describe a micro-anatomic pathway communicating a neural impulse between two neurons, wherein the two neurons form a focal anatomic association with one another.
  • the synaptic pathway includes a presynaptic neuron, the anatomic association comprising a synapse, and a postsynaptic neuron.
  • “Pharmacologic agent” means a biologically active substance delivered to the body with the intent to render a therapeutic effect on a tissue or organ.
  • Pharmacologic agents include any recognized drug and any substance used or acting as a drug.
  • “Stimulating” means delivering a physiologic provocation with the intent to activate a synapse.
  • “Cognitive training exercises” means an activity relating to or involving conscious intellectual activity, including but not limited to thinking, reasoning, or remembering.
  • Noninvasive brain imaging studies such as computed tomography and magnetic resonance imaging (MRI), demonstrate volume loss in the hippocampus of patients with chronic or chronically recurring depression.
  • Functional magnetic resonance imaging has been used to show micro-changes in blood flow within multiple regions of the brain in persons suffering from depression. These regions include the hippocampus, areas within the prefrontal cortex, basal ganglia, and limbic system. A corresponding decrease in synaptic density is also seen in these areas of depressed persons.
  • the methods described herein combine pharmacologic and stimulation therapies to achieve a surprising result — temporary improvements in mood and behavior experienced following initial treatment with a pharmacologic agent are made long-lasting by adding stimulation therapy.
  • This combination treatment has been named “synaptic pathway training” because the method “trains” a group of synaptic pathways activated by an initial treatment to continue functioning in the desired way by using regular and repeating neurologic stimulation.
  • Ketamine is a N-methyl-D-aspartate (NMD A) receptor antagonist with opioid receptor activity.
  • NMD A N-methyl-D-aspartate
  • the structure of ketamine comprises an aryl cyclohexylamine.
  • ketamine acts as a dissociative anesthetic.
  • anesthetic ketamine is rapid acting and has a short duration of action. Because moderate doses do not typically produce decreases in respiration or blood pressure, ketamine is useful in providing anesthesia in children and in various non-hospital settings.
  • Ketamine may be parenterally administered using an intravenous, intramuscular, or trans-nasal route.
  • ketamine by intravenous infusion at a dose of about 0.5 milligrams per kilogram of patient body weight (mg/kg) over between about forty-five (45) and about sixty (60) minutes is used to produce relief of symptoms of depression. Higher doses may be used, although doses of about 1.0 mg/kg intravenously over 45 to 60 minutes produces a state of sedation with vivid visual sensory changes. Patients who experience these vivid visual sensory changes, however, experience a stronger anti depressive effect of the treatment.
  • Administration of single-dose intravenous ketamine infusions is also associated with a transient increase in hippocampal volume corresponding with an increase in synaptic density.
  • hippocampal volume and synaptic density resulting from the administration of single-dose ketamine allows non-depressive thought patterns to occur.
  • This increase in hippocampal volume, synaptic pathways and synaptic density also lessens or eliminates the compulsion for an alcoholic to consume alcohol.
  • ketamine new synapses can be formed in the hippocampus along with the above-mentioned increases in volume and synaptic density.
  • the anti -depressant effects of ketamine persist from about seven (7) to about twenty- one (21) days, after which symptoms of depression or the urge to consume alcohol begin to re- emerge. If a second dose of ketamine is given by intravenous infusion usually six (6) days after the first dose, symptoms of depression or the urge to consume alcohol do not return until approximately twenty-eight (28) days after the second treatment. Treating depression or alcoholism with two doses of intravenous ketamine six days apart, therefore, may result in as much as approximately thirty-four (34) days of symptom relief.
  • Stimulation targeting the associated neural synaptic pathways activated by the ketamine results in a profound prolongation of symptom relief.
  • Stimulation may be intrinsic, extrinsic, or a combination of both.
  • “Intrinsic stimulation” is stimulation delivered to the synaptic pathway by the patient engaging in active cognition
  • “extrinsic stimulation” is the application of an external stimulus, the effects of which passively activate the synaptic pathway without any conscious participation by the patient.
  • a novel aspect of this method is using a pharmacologic agent in combination with a neural stimulation means, whether extrinsic or intrinsic, to subsequently target the brain area (synaptic pathway) activated by the pharmacologic agent.
  • a pharmacologic agent in combination with a neural stimulation means, whether extrinsic or intrinsic, to subsequently target the brain area (synaptic pathway) activated by the pharmacologic agent.
  • a pharmacologic agent in combination with a neural stimulation means, whether extrinsic or intrinsic, to subsequently target the brain area (synaptic pathway) activated by the pharmacologic agent.
  • ketamine may be used, depending on the synaptic pathway to be activated and the neurologic condition to be treated.
  • use of many different means of targeted stimulation of the activated synaptic pathways are also contemplated.
  • alcoholism as well as many neurologic conditions other than depression may be treated with a combination of pharmacologic synaptic pathway activation following by training the activated
  • FIG. 1 is a flowchart showing steps of a method for treating a neurologic condition using synaptic pathway training.
  • the neurologic condition is depression. “Depression” means either clinical diagnosis of either unipolar or bipolar depression. It should be understood, however, that treatment of many other neurologic conditions using method 100 is contemplated, including mental health conditions such as mania, post-traumatic stress disorder (“PTSD”), schizophrenia, dysthymia, chronic pain syndromes including complex regional pain syndrome, substance abuse disorders including but not limited to alcoholism, neuropathic pain, dysesthesia, traumatic brain injury, and other neurologic illnesses and conditions.
  • PTSD post-traumatic stress disorder
  • schizophrenia dysthymia
  • chronic pain syndromes including complex regional pain syndrome
  • substance abuse disorders including but not limited to alcoholism
  • neuropathic pain dysesthesia
  • traumatic brain injury and other neurologic illnesses and conditions.
  • FIG. 1 shows a method 100 comprising an activating step 110 and a stimulating step 120
  • Activating step 110 comprises activating a synaptic pathway with a pharmacologic agent.
  • the pharmacologic agent comprises an N- methyl-D-aspartate (NMDA) receptor antagonist.
  • NMDA N- methyl-D-aspartate
  • ketamine is an NMDA receptor antagonist used to activate various synaptic pathways associated with relieving symptoms and physical signs depression.
  • Ketamine, other NMDA receptor antagonists, and other pharmacologic agents also activate synaptic pathways of many other neurologic conditions, including but not limited to conditions noted herein above.
  • the pharmacologic agent in some embodiments, is used to activate synaptic pathways to treat any of these aforementioned of other neurologic conditions.
  • the pharmacologic agent is a serotonin receptor agonist, such as psilocybin, for example.
  • the pharmacologic agent is a muscarinic receptor agonist, such as scopolamine, for example.
  • Ketamine is administered at a standard dose of about 0.5 milligrams per kilogram body weight (“mg/kg”) as an intravenous infusion, in some embodiments.
  • the dose of intravenous ketamine is about 1.0 mg/kg.
  • the dose of intravenous ketamine is between about 0.5 mg/kg and about 1.0 mg/kg.
  • a relief of symptoms of depression indicates activation of the synaptic pathways targeted for training.
  • “Activation” of the synaptic pathway means an increase in the absolute number of functioning synaptic connections between axonal terminals of a presynaptic neuron and dendrites or cell bodies of one or more postsynaptic neurons.
  • the synaptic pathway is a prefrontal cortex synaptic pathway.
  • the synaptic pathway is a hippocampal synaptic pathway.
  • the synaptic pathway is a limbic system synaptic pathway.
  • the pharmacologic agent like ketamine, for example, causes an increase in synaptic density between the presynaptic and postsynaptic neurons of the synaptic pathway which correlates to relief from symptoms of depression, or some other neurologic condition including the urge to consume alcohol.
  • some patients experience a relief of depressive symptoms following one dose of intravenous ketamine.
  • Some patients do not experience a full relief of depression until receiving two doses of intravenous ketamine administered usually six (6) days apart.
  • Some patients require greater than two intravenous ketamine doses, each dose following the preceding dose by a period of one to two days. Consequently, in some embodiments, activating step 110 comprises administering two doses of the pharmacologic agent.
  • activating step 110 comprises administering three doses of the pharmacologic agent. In some embodiments, activating step 110 comprises administering greater than three doses of the pharmacologic agent.
  • the chosen dosage is effective in achieving a temporary dissociative state in the patient there will be an accompanying decrease or elimination of symptoms confirming the described positive changes to the hippocampus. This can be confirmed if necessary, by before and after scans.
  • the described cognitive exercises are initiated immediately after the first treatment to maintain the hippocampal changes for a period far beyond the time achieved with only the pharmacological treatment.
  • the length of time reduced or eliminated symptoms can be sustained will vary from patient to patient. Assuming adherence to the cognitive exercise protocol it is common to obtain an extension of the desired effect for twelve to eighteen months. As some point the symptoms will begin to gradually appear thus giving the patient time to notify their medical provided and obtain another pharmacological treatment followed by continued cognitive exercises.
  • brain mapping will correlate particular medical conditions such as those discussed above to particular areas of the brain.
  • Specific pharmacological drugs are then selected for treatment based upon their effect on the particular area which needs to be treated, namely increasing volume, synaptic pathways and synaptic density in the portion of the brain being treated.
  • the selected cognitive training exercise or external stimulation is chosen based upon the effect it has on the treated areas of the brain to maintain the increased volume, synaptic pathways and synaptic density.
  • Stimulating step 120 comprises stimulating the activated synaptic pathway.
  • stimulating step 120 acts to potentiate the activated state, but not to cause activation.
  • Stimulating synaptic or brain pathways that have been activated by prior treatment such as treatment with ketamine or another pharmacologic agent, for example, potentiate the favorable treatment result.
  • Activation of the synaptic pathway therefore, must be present for stimulating step 120 to have the intended effect of prolonging the relief of symptoms of the neurologic condition by prolonging the time period wherein the synaptic pathway remains activated.
  • stimulation of the activated synaptic pathway undertaken during stimulating step 120 may be intrinsic (cognitive) stimulation or extrinsic (sensory) stimulation.
  • Intrinsic (cognitive) stimulation is actively initiated by the patient.
  • Extrinsic (sensory) stimulation is passively received through an extrinsic sensory stimulus.
  • Cognitive stimulation is delivered to the activated synaptic pathway, in some embodiments, by performance of various cognitive exercises commonly known as “brain training” exercises.
  • the exercises include, but are not limited to, daily cognitive exercises performed for a minimum of about thirty (30) minutes to any longer time wherein the patient is able to focus on the activity.
  • Cognitive exercises comprise games and thought-activities designed to increase attention, memory, problem solving, focus, and the like.
  • An example of a cognitive exercise that may be utilized in stimulating step 120 is a proprietary set of exercises known as Brain HQ ® ” which has been shown to address the pathways resulting from Ketamine treatment for neurological disorders including but not limited to Bipolar and alcoholism
  • a non-limiting example of providing extrinsic stimulation includes placement of a potential voltage difference across the brain.
  • low-voltage direct current devices such as a transcranial direct-current stimulation device, may be used in some embodiments to provide an extrinsic stimulus to the activated synaptic pathway.
  • the electrodes to create the potential are positioned with a polarity to depolarize the pre- and post-synaptic neurons of the synaptic pathway.
  • extrinsic stimulation include placing the brain in a magnetic field.
  • the extrinsic stimulus comprises a sound.
  • the extrinsic stimulus comprises light.
  • the extrinsic stimulus comprises a tactile stimulus, such as a touch or a vibration delivered to an area of the body.
  • cognitive stimulation comprises periods of physical aerobic exercise. In some embodiments, the period of exercise is less than about twenty (20) minutes per day. In some embodiments, the period of exercise is between about twenty (20) and about forty- five (45) minutes per day. In some embodiments, the period of exercise is between about forty- five (45) minutes and about one (1) hour per day. In some embodiments, the period of exercise is greater than about one 1) hour per day.
  • FIG. 2 is a flowchart showing steps of a method for treating a neurologic condition using synaptic pathway training. As shown by FIG. 2, method 200 comprises a treating step 210 and an extending step 220.
  • Neurologic conditions successfully treated using method 200 include depression, bipolar disorder, alcoholism, mania and PTSD.
  • Use of method 200 is effective, durable, and does not create any of the side-effects associated with long-term therapy with pharmacologic agents, ECT, or other currently available treatments.
  • ketamine is used as the synaptic pathway altering agent, relief from sleep disorders — particularly insomnia — which accompany depression, mania, and PTSD is immediate and persists for months, so long as regular stimulation of the activated synaptic pathway undertaken in the extending step continues.
  • the use of method 200 to treat mania or the manic component of bipolar disease is particularly effective.
  • Method 200 is dramatically effective for the treatment of mania, in some persons, and none of the aforementioned side effects have been observed.
  • Method 200 is particularly useful in treating persons with PTSD, for at least four reasons.
  • First, method 200 is an effective treatment for PTSD.
  • Second, initial activation of the synaptic pathway may be accomplished immediately, essentially, during the treating step.
  • Third, means for provision of regular stimulation to the activated synaptic pathway, particularly intrinsic cognitive means, are readily available in field-settings, including some battlefield settings.
  • TBI Traumatic Brain Injury
  • Use of method 200 therefore, is particularly efficacious for use during deployment, where rapid, simple, and durable treatment of PTSD and PTSD/TBI in a soldier is essential.
  • Treating step 210 comprises treating the neurologic condition with a pharmacologic agent to alter a synaptic pathway.
  • the neurologic condition may be depression, bipolar disease, dysthymia, or any number of other neurologic conditions including, but not limited to, those neurologic conditions listed herein.
  • Treating means administering one or more therapies over one or more discrete time periods with the intent to either treat the condition, cure the condition, or relieve symptoms caused by the condition.
  • the therapies may comprise: administration of a pharmacologic agent; administration of a treatment, such as transcranial direct-current stimulation; or the like.
  • Alteration of the synaptic pathway means “activation” of the pathway manifest directly by an increase in synaptic density, or manifest indirectly by relief of improvement of symptoms of the neurologic condition.
  • Extending step 220 comprises extending a treatment result by repeatedly stimulating the synaptic pathway with a neural stimulating means. “Extending a treatment result” means causing the favorable results of treatment resulting from treating step 210 to remain manifest for a period of time longer than that period absent extending step 220.
  • extending step 220 comprises stimulating an activated synaptic pathway with an intrinsic stimulus, as described herein.
  • extending step 220 comprises stimulating an activated synaptic pathway with an extrinsic stimulus, as described herein.
  • extending step 220 comprises performance of physical exercise during recurring periods, such as daily, for a period of days, weeks, or months.
  • FIG. 3 is a flowchart showing steps of another method for treating a neurological condition using synaptic pathway training.
  • FIG. 3 shows a method 300 for treating a neurological condition comprising an activating step 310 and a stimulating step 320.
  • the neurologic condition is depression.
  • the neurological condition is mania or bipolar disease.
  • the neurological condition is PTSD.
  • activating step 310 comprises activating a synaptic pathway by administering at least one dose of ketamine, at least 0.5 mg/kg.
  • This is a baseline dose, which may need to be repeated one or more times, at intervals of about one to two (1-2) days. It is foreseeable that some patients would respond more readily to a higher dose, up to the 1.0 mg/kg dose which is typically used to induce a dissociated state of anesthesia.
  • the dose may need to be repeated two, three, or more times to obtain the desired level of relief. Relief of symptoms is the clinical marker which indicates activation of the synaptic pathway following completion of activating step 310, prior to performing stimulating step 320.
  • stimulating step 320 comprises stimulating the activated synaptic pathway by performing a cognitive exercise for at least thirty (30) minutes each day.
  • FIG. 4 is a flowchart showing steps of another method for treating a neurological condition using synaptic pathway training.
  • FIG. 4 shows a method 400 for treating a neurological condition comprising initially consulting with a patient to be treated the medical provider will start by diagnosing the issue step 410. Once diagnosed the area of the brain most related to that issue is identified step 420.
  • the pharmacological treatment including but not limited to a dissociative or hallucinogenic which creates a positive effect on that potion of the brain by increasing synaptic pathways and synaptic density (synaptic volume) is selected step 430.
  • a therapeutic dosage is selected to achieve and increase in structures such as volume, synaptic pathways and synaptic density step 440 and administered to the patient step 450.
  • a regimen of nonpharmacological brain stimulus is selected that effects the targeted area of the brain to maintain the increased structural changes step 460, and the brain stimulus training is initiated step 470.
  • Observation of and discussions with the patient determines whether the dosage was sufficient to achieve patient experience step 480 indicating the desired increases in structure step 490.

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Abstract

Sont divulguées des méthodes de traitement de la dépression, de la manie, du trouble du stress post-traumatique (PTSD) et de diverses autres affections neurologiques au moyen d'un entraînement de voie synaptique. Les méthodes d'entraînement de voie synaptique comprennent, en général, l'obtention d'un résultat de traitement favorable par activation d'une voie synaptique à l'aide d'un agent pharmacologique, tel que le traitement de symptômes réfractaires de la dépression par la kétamine, suite à la potentialisation du résultat favorable par stimulation répétée de la voie activée. La stimulation d'une voie synaptique peut être obtenue par des moyens intrinsèques, tels que l'activation de la fonction cognitive exercée, ou des moyens extrinsèques, tels que l'administration d'un stimulus sensoriel au patient, la mise en place d'une différence de tension potentielle à travers le cerveau ou une région cérébrale, ou en plaçant le cerveau ou une région cérébrale dans un champ magnétique.
PCT/US2021/022517 2020-03-23 2021-03-16 Méthode de traitement de troubles neurologiques à l'aide d'un entraînement de voie synaptique WO2021194796A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
IL296693A IL296693A (en) 2020-03-23 2021-03-16 A method for treating neurological disorders using synaptic pathway training
CA3172981A CA3172981A1 (fr) 2020-03-23 2021-03-16 Methode de traitement de troubles neurologiques a l'aide d'un entrainement de voie synaptique
MX2022011862A MX2022011862A (es) 2020-03-23 2021-03-16 Combinacion de un agente farmacologico y un agente de tratamiento no farmacologico para el tratamiento de trastornos neurologicos mediante entrenamiento de vias sinapticas.
BR112022019234A BR112022019234A2 (pt) 2020-03-23 2021-03-16 Método para tratamento de transtornos neurológicos usando treinamento de via sináp-tica
EP21776197.2A EP4126199A4 (fr) 2020-03-23 2021-03-16 Méthode de traitement de troubles neurologiques à l'aide d'un entraînement de voie synaptique
ZA2022/10356A ZA202210356B (en) 2020-03-23 2022-09-19 Method for treatment of neurological disorders using synaptic pathway training

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IL296693A (en) 2022-11-01
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