Neuroprotection in Demyelinating Diseases
Methods of treating neurological disorders, e.g., those characterized by demyelination and/or axonal loss (e.g., MS), are provided. The methods comprise administration of 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; and either glatiramer acetate or interferon-beta.
1 - 50 . (canceled)
51 . A method of treating a subject having multiple sclerosis (MS), the method consisting essentially of:
(a) administering to the subject 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, optionally in combination with one or more pharmaceutically acceptable excipients; and
(b) administering to the subject a therapeutically effective amount of glatiramer acetate, optionally in combination with one or more pharmaceutically acceptable excipients.
52 . The method of claim 51 , wherein the MS is selected from relapsing remitting MS, secondary progressive MS, primary progressive MS, progressive relapsing MS, and clinically isolated syndrome.
53 . The method of claim 51 , wherein the at least one compound of Formula I is chosen from dimethyl fumarate (DMF), monomethyl fumarate (MMF), and combinations thereof.
54 . The method of claim 53 , wherein the at least one compound of Formula I is DMF.
55 . The method of claim 54 , wherein about 240 mg of DMF is administered to the subject at one time.
56 . The method of claim 55 , wherein the DMF is administered to the subject two times per day (BID) equivalent to a total daily dose of about 480 mg/day.
57 . The method of claim 51 , wherein about 20 mg/day of glatiramer acetate is administered to the subject.
58 . The method of claim 51 , wherein less than about 20 mg/day of glatiramer acetate is administered to the subject.
59 . The method of claim 51 , wherein the compound of Formula I and the glatiramer acetate are administered in amounts and for periods of time sufficient to reduce a relapse rate in the subject.
60 . The method of claim 51 , wherein the compound of Formula I and the glatiramer acetate are administered in amounts and for periods of time sufficient to reduce demyelination and/or axonal death in the subject.
61 . A method of treating a subject having multiple sclerosis (MS), the method comprising:
(a) administering to the subject 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; and
(b) administering to the subject a therapeutically effective amount of glatiramer acetate;
wherein the compound of Formula I and the glatiramer acetate are the only active agents administered to said subject for said treating.
62 . The method of claim 61 , wherein the MS is selected from relapsing remitting MS, secondary progressive MS, primary progressive MS, progressive relapsing MS, and clinically isolated syndrome.
63 . The method of claim 61 , wherein the at least one compound of Formula I is chosen from dimethyl fumarate (DMF), monomethyl fumarate (MMF), and combinations thereof.
64 . The method of claim 63 , wherein the at least one compound of Formula I is DMF.
65 . The method of claim 64 , wherein about 240 mg of DMF is administered to the subject at one time.
66 . The method of claim 65 , wherein the DMF is administered to the subject two times per day (BID) equivalent to a total daily dose of about 480 mg/day.
67 . The method of claim 61 , wherein about 20 mg/day of glatiramer acetate is administered to the subject.
68 . The method of claim 61 , wherein less than about 20 mg/day of glatiramer acetate is administered to the subject.
69 . The method of claim 61 , wherein the compound of Formula I and the glatiramer acetate are administered in amounts and for periods of time sufficient to reduce a relapse rate in the subject.
70 . The method of claim 61 , wherein the compound of Formula I and the glatiramer acetate are administered in amounts and for periods of time sufficient to reduce demyelination and/or axonal death in the subject.
71 . The method of claim 52 , wherein the MS is relapsing remitting MS.
72 . The method of claim 54 , wherein the MS is relapsing remitting MS.
73 . The method of claim 62 , wherein the MS is relapsing remitting MS.
74 . The method of claim 64 , wherein the MS is relapsing remitting MS.