NRF2 Screening Assays and Related Methods and Compositions

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.

1 .- 17 . (canceled) 
     
     
         18 . A method of treating amyotrophic lateral sclerosis (ALS), comprising orally administering to a subject in need of such treatment a therapeutically effective amount of dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination thereof. 
     
     
         19 . The method of  claim 18 , wherein the therapeutically effective amount is administered in separate administrations of 2, 3, 4, or 6 equal doses. 
     
     
         20 . The method of  claim 19 , wherein the therapeutically effective amount is administered to the subject in separate administrations of 2 equal doses. 
     
     
         21 . The method of  claim 19 , wherein the therapeutically effective amount is administered in separate administrations of 3 equal doses. 
     
     
         22 . The method of  claim 18 , wherein the therapeutically effective amount of DMF, MMF, or a combination thereof is from about 200 mg to about 800 mg per day. 
     
     
         23 . The method of  claim 18 , wherein the therapeutically effective amount of DMF, MMF, or a combination thereof is from about 480 mg to about 720 mg per day. 
     
     
         24 . The method of  claim 18 , wherein the expression level of NQO1 in the subject is elevated after administering to the subject the therapeutically effective amount of DMF, MMF, or a combination thereof. 
     
     
         25 . A method of treating amyotrophic lateral sclerosis (ALS), comprising orally administering to a subject in need of such treatment a therapeutically effective amount of DMF. 
     
     
         26 . The method of  claim 25 , wherein the DMF is administered in separate administrations of 2 equal doses. 
     
     
         27 . The method of  claim 25 , wherein the DMF is administered in separate administrations of 3 equal doses. 
     
     
         28 . The method of  claim 25 , wherein the therapeutically effective amount of DMF is from about 200 mg to about 800 mg per day. 
     
     
         29 . The method of  claim 25 , wherein the therapeutically effective amount of DMF is from about 480 mg to about 720 mg per day. 
     
     
         30 . The method of  claim 25 , wherein the expression level of NQO1 in the subject is elevated, after administering to the subject the therapeutically effective amount of DMF.