Neuroprotection in Demyelinating Diseases
Methods of treating neurological disorders characterized by extensive demyelination and/or axonal loss are provided. Examples of such disorders include secondary progressive multiple sclerosis and Devic's disease. The disclosed methods include administering to a subject having such a disorder a therapeutically effective amount of, for example, dimethyl fumarate or monomethyl fumarate.
1 . A method of treating a subject in need of treatment for a progressive form of multiple sclerosis, the method comprising administering to the subject in need thereof, a therapeutically effective amount of at least one compound of Formula I:
wherein R 1 and R 2 are independently selected from OH, O − , and (C 1-6 )alkoxy, or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein he compound is chosen from dimethyl fumarate and monomethyl fumarate.
3 .- 7 . (canceled)
8 . The method of claim 1 , wherein the subject has secondary progressive multiple sclerosis.
9 . (canceled)
10 . The method of claim 1 , wherein the subject exhibits at least a 1-point increase on the EDSS over a period of one year prior to the administration of the compound.
11 . The method of claim 1 , wherein the subject exhibits at least a 25% increase in T1 lesion load over a period of one year prior to the administration of the compound.
12 . The method of claim 1 , wherein the subject has an EDSS score of at least 3.
13 . The method of claim 1 , wherein the subject has more than 10 hypointense T1 lesions.
14 . (canceled)
15 . The method of claim 1 , wherein the subject has primary progressive multiple sclerosis.
16 . The method of claim 1 , wherein the subject has an EDSS score of more than 5.
17 . The method of claim 2 , wherein the compound is administered orally.
18 . The method of claim 17 , wherein the therapeutically effective amount is from about 200 mg to about 800 mg per day.
19 . The method of claim 17 , wherein the therapeutically effective amount is from about 480 mg to about 720 mg per day.
20 . The method of claim 17 , wherein the therapeutically effective amount is about 480 mg per day.
21 . The method of claim 17 , wherein the therapeutically effective amount is about 720 mg per day.
22 . The method of claim 17 , wherein the therapeutically effective amount is administered to the subject in separate administrations of 2, 3, 4, or 6 equal doses.
23 . The method of claim 22 , wherein the therapeutically effective amount is administered to the subject in separate administrations of 2 equal doses.
24 . The method of claim 22 , wherein the therapeutically effective amount is administered in separate administrations of 3 equal doses.
25 . The method of claim 1 , wherein the compound is dimethyl fumarate.
26 . The method of claim 1 , wherein the compound is monomethyl fumarate.
27 . The method of claim 1 , wherein the method comprises orally administering to the subject one or more capsule(s) containing a pharmaceutical preparation consisting essentially of 60 to 240 mg of dimethyl fumarate.
28 . The method of claim 27 , wherein the method comprises orally administering to the subject one or more capsule(s) containing a pharmaceutical preparation consisting essentially of 120 mg of dimethyl fumarate.
29 . The method of claim 1 , wherein the compound is orally administered to the subject in the form of pills, tablets, microtablets, pellets, micropellets, capsules, capsules containing microtablets, or liquid formulations.
30 . The method of claim 1 , wherein the compound is administered to the subject in the form of a sustained or controlled release formulation.