Treatment for multiple sclerosis

• US 8,399,514 B2
• Filed: 02/13/2012
• Issued: 03/19/2013
• Est. Priority Date: 02/08/2007
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Lukashev, Matvey E., O'Neill, Gilmore
• Primary Examiner(s): ULM, JOHN D
• Application Number:
  US13/372,426
• Publication Number:
  US 20120196931A1
• Time in Patent Office: 400 Days
• Field of Search: None
• US Class Current: 514/549
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/197 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 carnitine A61K31/205
• CPC Class Codes: A61K 31/225 Polycarboxylic acids
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 38/217 IFN-gamma
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 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 Class Codes: G01N 2333/90209 acting on NADH or NADPH (1.6), e.g. those with a heme protein as acceptor (1.6.2) (general), Cytochrome-b5 reductase (1.6.2.2) or NADPH-cytochrome P450 reductase (1.6.2.4)
• CPC Class Codes: G01N 2800/285 Demyelinating diseases; Multipel sclerosis
• CPC Class Codes: G01N 33/502 for testing non-proliferative effects
• CPC Class Codes: G01N 33/5041 involving analysis of members of signalling pathways

Abstract

Provided are certain methods of screening, identifying, and evaluating neuroprotective compounds useful for treatment of neurological diseases, such as, e.g., multiple sclerosis (MS). The compounds described upregulate the cellular cytoprotective pathway regulated by Nrf2. Also provided are certain methods of utilizing such compounds in therapy for neurological disease, particularly, for slowing or reducing demyelination, axonal loss, or neuronal and oligodendrocyte death.

Claims

1. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.

2. The method of claim 1, wherein the pharmaceutical composition is administered in the form of a tablet, a suspension, or a capsule.

3. The method of claim 1, wherein the therapeutically effective amount is administered in separate administrations of 2, 3, 4, or 6 equal doses.

4. The method of claim 3, wherein the therapeutically effective amount is administered in separate administrations of 2 equal doses.

5. The method of claim 3, wherein the therapeutically effective amount is administered in separate administrations of 3 equal doses.

6. The method of claim 1, wherein the pharmaceutical composition consists essentially of dimethyl fumarate and one or more pharmaceutically acceptable excipients.

7. The method of claim 1, wherein the pharmaceutical composition consists essentially of monomethyl fumarate and one or more pharmaceutically acceptable excipients.

8. The method of claim 1, wherein the pharmaceutical composition is administered to the subject for at least 12 weeks.

9. The method of claim 6, wherein the therapeutically effective amount is administered to the subject in 2 equal doses.

10. The method of claim 9, wherein the therapeutically effective amount is administered to the subject for at least 12 weeks.

17. The method of claim 1, wherein the expression level of NQO1 in the subject is elevated after administering to the subject the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof.

11. A method of treating a subject in need of treatment for multiple sclerosis consisting essentially of orally administering to the subject about 480 mg per day of dimethyl fumarate, monomethyl fumarate, or a combination thereof.

12. The method of claim 11, wherein about 480 mg of dimethyl fumarate per day is administered to the subject.

13. The method of claim 12, wherein the dimethyl fumarate is administered in separate administrations of 2 equal doses.

14. The method of claim 12, wherein the dimethyl fumarate is administered in separate administrations of 3 equal doses.

18. The method of claim 11, wherein the expression level of NQO1 in the subject is elevated after administering to the subject about 480 mg per day of dimethyl fumarate, monomethyl fumarate, or a combination thereof.

15. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate is about 480 mg per day.

16. The method of claim 15, wherein the dimethyl fumarate is administered in separate administrations of 2 equal doses.

19. The method of claim 15, wherein the expression level of NQO1 in the subject is elevated after administering to the subject the therapeutically effective amount of dimethyl fumarate.

20. A method of treating a subject in need of treatment for multiple sclerosis comprising treating the subject in need thereof with a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.