WO2015033224A2 - Méthodes de traitement du syndrome de l'x fragile et de troubles associés - Google Patents

Méthodes de traitement du syndrome de l'x fragile et de troubles associés Download PDF

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Publication number
WO2015033224A2
WO2015033224A2 PCT/IB2014/002398 IB2014002398W WO2015033224A2 WO 2015033224 A2 WO2015033224 A2 WO 2015033224A2 IB 2014002398 W IB2014002398 W IB 2014002398W WO 2015033224 A2 WO2015033224 A2 WO 2015033224A2
Authority
WO
WIPO (PCT)
Prior art keywords
metadoxine
mice
treatment
fmrl knockout
administration
Prior art date
Application number
PCT/IB2014/002398
Other languages
English (en)
Other versions
WO2015033224A3 (fr
Inventor
Yaron DANIELY
Dalia Megiddo
Original Assignee
Alcobra Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US14/038,258 external-priority patent/US20150073023A1/en
Priority to EP14830858.8A priority Critical patent/EP3043792A2/fr
Priority to JP2016539645A priority patent/JP2016530291A/ja
Priority to KR1020167009040A priority patent/KR20160078956A/ko
Priority to CN201480049671.5A priority patent/CN105517546A/zh
Priority to EA201690557A priority patent/EA201690557A1/ru
Application filed by Alcobra Ltd. filed Critical Alcobra Ltd.
Priority to SG11201601605YA priority patent/SG11201601605YA/en
Priority to AU2014316779A priority patent/AU2014316779A1/en
Priority to MX2016003006A priority patent/MX2016003006A/es
Priority to US14/917,169 priority patent/US9851354B2/en
Priority to CA2922901A priority patent/CA2922901A1/fr
Publication of WO2015033224A2 publication Critical patent/WO2015033224A2/fr
Publication of WO2015033224A3 publication Critical patent/WO2015033224A3/fr
Priority to IL244343A priority patent/IL244343A0/en

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the metadoxme or acceptable derivative thereof may be formulated for immediate release upon administration to the subject.
  • the metadoxme or acceptable derivative thereof may be formulated for sustained and/or controlled release, and may optionally be formulated to have both immediate release and sustained and/or controlled release
  • an embodiment of the method of the present invention is to administer the therapeutic compound described herein in a sustained release form.
  • Any controlled or sustained release method known to those of ordinary skill in the art may be used with the compositions and methods of the invention such as those described in Langer, Science 249(4976): 1527-33 ( 1990).
  • Such method comprises administering a sustained-release composition, a suppository, or a coated implantable medical device so that a therapeutically effective dose of the composition of the invention is continuously delivered to a subject of such a method.
  • the metadoxine or metadoxine derivative in compositions used by the invention may be formulated for sustained or controlled release over a period of between about 0.5 or 1 or 2 or 3 or 4 hours and about 5, 6, 7, 8, 9, 10, 1 1 or 12 hours. In certain embodiments, the metadoxine or metadoxine derivative in compositions used by the invention may be formulated for sustained or controlled release over a period of between about 5 or 6 or 7 or 8 hours and about 9, 10, 11 or 12 hours.
  • the metadoxine or metadoxine derivative in compositions used by the invention may be formulated to release up to 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, 99.5 or 100% of the total metadoxine or metadoxine derivative in about 0.5, 1, 2, 3, 4, 5, 6, 7 or 8 hours.
  • metadoxine or metadoxine derivatives formulations of the present invention may be administered in a sufficient amount to produce a reasonable benefit/risk ratio applicable to a selected treatment, as may be determined by the skilled artisan.
  • salt adducf is meant to encompass a salt product of a direct addition of two or more distinct ions, wherein the overall charge of the salt adduct is zero.
  • the salt adduct comprises one positively charged moiety having a single positive charge functional group (i.e., the positively charged moiety is charged with H- 1 net charge) and one negatively charged moiety having a single negative charge functional group (i.e., the negatively charged moiety is charged with -1 net charge).
  • the salt adduct comprises a positively charged moiety charged with +n net charge (originating from one or more positively charged functional groups, which may be the same or different), and a negatively charge moiety having -n (originating from one or more negatively charged functional groups, which may be the same or different) net charge, wherein n is an integer which may be equal to 1 , 2, 3, 4, 5 or 6.
  • the successive alleys test effectively measured anxiety (latency to enter the Alley 1 ) and hyperactivity (Alleys 2 to 4). Progression from Alley 1 through the successive Alleys 2, 3, and 4 was associated with exposure to an increasingly brightly colored environment with increasingly lower wails and narrower, more exposed open arms. Time spent on, and entries into, the open arms indicated anxiety; conversely, increasing time spent in more open arms reflected hyperactivity. These factors allowed for a sensitive test bracketing a range of anxiety-like behaviors together with hyperactivity.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Steroid Compounds (AREA)

Abstract

La présente invention concerne des méthodes d'atténuation d'un signe ou d'un symptôme du syndrome de l'X fragile et concerne des troubles tels que des troubles du spectre de l'autisme.
PCT/IB2014/002398 2013-09-09 2014-09-09 Méthodes de traitement du syndrome de l'x fragile et de troubles associés WO2015033224A2 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CA2922901A CA2922901A1 (fr) 2013-09-09 2014-09-09 Methodes de traitement du syndrome de l'x fragile et de troubles associes
AU2014316779A AU2014316779A1 (en) 2013-09-09 2014-09-09 Methods of treating fragile X Syndrome and related disorders
KR1020167009040A KR20160078956A (ko) 2013-09-09 2014-09-09 취약 x 증후군 및 관련 장애의 치료 방법
CN201480049671.5A CN105517546A (zh) 2013-09-09 2014-09-09 治疗脆性x综合征及相关疾病的方法
EA201690557A EA201690557A1 (ru) 2013-09-09 2014-09-09 Способы лечения синдрома ломкой х-хромосомы и связанных расстройств
EP14830858.8A EP3043792A2 (fr) 2013-09-09 2014-09-09 Méthodes de traitement du syndrome de l'x fragile et de troubles associés
SG11201601605YA SG11201601605YA (en) 2013-09-09 2014-09-09 Methods of treating fragile x syndrome and related disorders
JP2016539645A JP2016530291A (ja) 2013-09-09 2014-09-09 脆弱ｘ症候群および関連障害の処置方法
MX2016003006A MX2016003006A (es) 2013-09-09 2014-09-09 Metodos para tratar el sindrome de x fragil y trastornos relacionados.
US14/917,169 US9851354B2 (en) 2013-09-09 2014-09-09 Methods of treating fragile X syndrome and related disorders
IL244343A IL244343A0 (en) 2013-09-09 2016-02-29 Methods for the treatment of fragile x syndrome and related disorders

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201361875384P 2013-09-09 2013-09-09
US61/875,384 2013-09-09
US14/038,258 2013-09-26
US14/038,258 US20150073023A1 (en) 2013-09-09 2013-09-26 Method Of Treating Fragile X Syndrome And Related Disorders
US201461991351P 2014-05-09 2014-05-09
US61/991,351 2014-05-09

Publications (2)

Publication Number Publication Date
WO2015033224A2 true WO2015033224A2 (fr) 2015-03-12
WO2015033224A3 WO2015033224A3 (fr) 2015-07-02

Family

ID=52629036

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/IB2014/002398 WO2015033224A2 (fr) 2013-09-09 2014-09-09 Méthodes de traitement du syndrome de l'x fragile et de troubles associés
PCT/US2014/054816 WO2015035402A1 (fr) 2013-09-09 2014-09-09 Procédés de détermination d'une réponse à un traitement

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2014/054816 WO2015035402A1 (fr) 2013-09-09 2014-09-09 Procédés de détermination d'une réponse à un traitement

Country Status (12)

Country Link
EP (2) EP3043792A2 (fr)
JP (2) JP2016530536A (fr)
KR (2) KR20160078956A (fr)
CN (2) CN105917225A (fr)
AU (2) AU2014316779A1 (fr)
CA (2) CA2923421A1 (fr)
EA (2) EA201690557A1 (fr)
IL (2) IL244343A0 (fr)
MX (2) MX2016003002A (fr)
SG (2) SG11201601830PA (fr)
TW (2) TW201605443A (fr)
WO (2) WO2015033224A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9851354B2 (en) 2013-09-09 2017-12-26 Alcobra Ltd. Methods of treating fragile X syndrome and related disorders

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3239161A1 (fr) * 2013-07-31 2017-11-01 UDC Ireland Limited Complexes de carbène-métal diazabenzimidazole luminescent
CN108538365A (zh) * 2017-03-24 2018-09-14 华东师范大学 一种基于数据分析技术的自闭症社交能力评估系统
CN112055587A (zh) * 2018-04-13 2020-12-08 Healx有限公司 脆性x综合征的治疗
KR20190121569A (ko) * 2018-04-18 2019-10-28 건국대학교 글로컬산학협력단 아그마틴 및 이의 약학적으로 허용 가능한 염을 포함하는 취약 x 증후군 예방 또는 치료용 약학조성물
AU2019280980A1 (en) * 2018-06-07 2021-01-07 Ovid Therapeutics Inc. Use of (S)-3-amino-4-(difluoromethylenyl) cyclopent-1-ene-1-carboxylic acid and related compounds, (1S,3S)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid and vigabatrin in the treatment of developmental disorders
WO2021141426A1 (fr) * 2020-01-08 2021-07-15 건국대학교 글로컬산학협력단 Composition de traitement du syndrome de l'x fragile ou des troubles du développement associés, comprenant un composé de lisuride en tant que principe actif
CN115397414A (zh) * 2020-02-07 2022-11-25 株式会社纽若梵提 包含利美尼定的用于治疗脆性x染色体综合征的组合物

Citations (2)

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US4313952A (en) 1980-06-30 1982-02-02 Massimo Baldacci Method of treating acute alcoholic intoxication with pyridoxine P.C.A.
WO2009004629A2 (fr) 2007-07-03 2009-01-08 Alcobra Ltd. Procédé pour réduire les symptômes de consommation d'alcool

Family Cites Families (2)

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Publication number Priority date Publication date Assignee Title
US20020155170A1 (en) * 2000-11-30 2002-10-24 Walsh William John Nutrient supplements and methods for treating autism and for preventing the onset of autism
EP2445498A1 (fr) * 2009-06-25 2012-05-02 Alcobra Ltd. Procédé pour le traitement, l'atténuation de symptômes et le soulagement, l'amélioration et la prévention d'une maladie, d'un trouble ou d'un état cognitif

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4313952A (en) 1980-06-30 1982-02-02 Massimo Baldacci Method of treating acute alcoholic intoxication with pyridoxine P.C.A.
WO2009004629A2 (fr) 2007-07-03 2009-01-08 Alcobra Ltd. Procédé pour réduire les symptômes de consommation d'alcool

Non-Patent Citations (5)

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Title
"Remington's Pharmaceutical Sciences", 1990, MACK PUB.
LANGER, SCIENCE, vol. 249, no. 4976, 1990, pages 1527 - 33
LU YUAN ET AL., CHIN. MED. 1, vol. 120, no. 2, 2007, pages 160 - 168
LU YUAN ET AL., CHIN. MED. J, vol. 120, no. 2, 2007, pages 160 - 168
MCCRACKEN, J. T. ET AL., N. ENGL. J. MED., vol. 347, 2002, pages 314 - 321

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9851354B2 (en) 2013-09-09 2017-12-26 Alcobra Ltd. Methods of treating fragile X syndrome and related disorders
US9851355B2 (en) 2013-09-09 2017-12-26 Alcobra Ltd. Methods of determining response to therapy

Also Published As

Publication number Publication date
IL244343A0 (en) 2016-04-21
CA2922901A1 (fr) 2015-03-12
WO2015033224A3 (fr) 2015-07-02
CA2923421A1 (fr) 2015-03-12
TW201605443A (zh) 2016-02-16
EA201690559A1 (ru) 2016-08-31
JP2016530291A (ja) 2016-09-29
CN105917225A (zh) 2016-08-31
MX2016003006A (es) 2016-06-10
EP3044589A1 (fr) 2016-07-20
SG11201601605YA (en) 2016-04-28
MX2016003002A (es) 2016-09-08
AU2014315026A1 (en) 2016-03-24
EP3043792A2 (fr) 2016-07-20
IL244453A0 (en) 2016-04-21
WO2015035402A1 (fr) 2015-03-12
TW201606304A (zh) 2016-02-16
KR20160078956A (ko) 2016-07-05
SG11201601830PA (en) 2016-04-28
CN105517546A (zh) 2016-04-20
AU2014316779A1 (en) 2016-03-17
EA201690557A1 (ru) 2016-07-29
KR20160086818A (ko) 2016-07-20
JP2016530536A (ja) 2016-09-29

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