Methods of treating developmental disorders with biguanides

Patent metadata

Field	Value
Publication number	US-10426746-B2
Application number	US-201816157653-A
Country	US
Kind code	B2
Filing date	Oct 11, 2018
Priority date	Aug 18, 2016
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

Methods of treating developmental disorders such as Angelman syndrome, Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Autistic Spectrum Disorder, Autism, Asperger's syndrome, pervasive developmental disorder, Childhood Disintegrative Disorder, Rett syndrome, Landau-Kleffner Syndrome, Prader-Willi Syndrome, Tardive Dyskinesia, a seizure disorder and/or Williams Syndrome with a biguanide such as metformin, buformin, phenformin or a pharmaceutically acceptable salt thereof are provided. The methods provide therapeutic compositions that may be used to improve one or more symptoms of the developmental disorder.

First claim

What is claimed is:

1. A method of treating Fragile X syndrome comprising administering to a patient in need thereof a therapeutically effective amount of a biguanide or a pharmaceutically acceptable salt thereof, the biguanide selected from the group consisting of metformin, buformin and phenformin, wherein the method provides improvement in one or more symptoms of Fragile X syndrome in the patient.

2. The method of claim 1 , wherein the patient is administered from about 50 mg to about 3000 mg metformin or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the patient is administered from about 500 mg to about 2500 mg metformin or a pharmaceutically acceptable salt thereof in a 24 hour period.

4. The method of claim 1 , wherein the patient is administered from about 10 mg to about 500 mg buformin or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the patient is administered from about 10 mg to about 500 mg buformin or a pharmaceutically acceptable salt thereof in a 24 hour period.

6. The method of claim 1 , wherein the patient is administered from about 10 mg to about 300 mg phenformin or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the patient is administered from about 10 mg to about 300 mg phenformin or a pharmaceutically acceptable salt thereof in a 24 hour period.

8. The method of claim 1 , wherein the in vivo plasma profile of the patient 10 hours after administration of the biguanide or pharmaceutically acceptable salt thereof is reduced by more than 50% and the method provides improvement in next day functioning of the patient.

9. The method of claim 1 , wherein the in vivo plasma profile of the patient 10 hours after administration of the biguanide or pharmaceutically acceptable salt thereof is reduced by more than 50% and the method provides improvement in the patient for more than 10, 12, 14, 16, 18, 20, 22 or 24 hours after administration.

10. The method of claim 1 , wherein the method provides improvement in at least one symptom selected from the group consisting of ataxia, gait, speech impairment, vocalization, cognition, motor activity, clinical seizure, subclinical seizure, hypotonia, hypertonia, feeding difficulty, drooling, mouthing behavior, sleep difficulties, repetitive hand movements, hand flapping, hand ringing, shakiness of the torso, apnea, hyperventilation and air swallowing, muscle rigidity, spasticity, teeth grinding, poor circulation of the lower extremities, easily provoked laughter and short attention span.

11. The method of claim 1 , wherein the method provides improvement in the patient for more than 6 hours.

12. The method of claim 1 , wherein the method provides improvement in the patient for more than 8 hours.

13. The method of claim 1 , wherein the method provides improvement in the patient for at least 12 hours.

14. The method of claim 1 , wherein a composition containing from about 10 mg to about 1000 mg of the biguanide or a pharmaceutical salt thereof is administered to the patient.

15. The method of claim 14 , wherein a composition containing from about 500 mg to about 1000 mg of metformin or a pharmaceutical salt thereof is administered to the patient.

16. The method of claim 14 , wherein the composition contains 500 mg, 850 mg or 1000 mg of metformin hydrochloride.

17. The method of claim 14 , wherein the composition contains 500 mg or 750 mg of metformin hydrochloride.

18. The method of claim 14 , wherein the composition is an extended release dosage form.

19. The method of claim 14 , wherein the composition is a delayed release dosage form.

20. The method of claim 14 , wherein the composition is an immediate release dosage form.

21. The method of claim 14 , wherein the composition is a conventional release dosage form.

Assignees

• Ovid Therapeutics Inc

Inventors

• During Matthew

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61K31/155 Primary

  Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2) · CPC title

• C07C279/26

  X and Y being nitrogen atoms, i.e. biguanides · CPC title