Identification of compounds that disperse tdp-43 inclusions

Abstract

Herein, compounds and compositions for use in treating diseases relating to inclusion formation and stress granules are described. Methods for screening for modulation of TDP-43 aggregation are also described.

1 - 36 . (canceled) 
     
     
         37 . A method of treating a neurodegenerative disease or a viral infection in a subject in need thereof, the method comprising administering an effective amount of a compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         38 . The method of  claim 37 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The method of  claim 37 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The method of  claim 37 , wherein the neurodegenerative disease is selected from Alzheimer's disease, frontotemporal dementia, FTLD-U, amyotrophic lateral sclerosis (ALS), Huntington's chorea, Creutzfeld-Jacob disease, trinucleotide repeat diseases, cerebral degenerative diseases presenile dementia, senile dementia, Parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy (PSP), Huntington's disease (HD), Pick's disease, primary progressive aphasia, corticobasal dementia, Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies, Down's syndrome, multiple system atrophy, spinal muscular atrophy (SMA), spinocerebellar ataxia, spinal degenerative disease/motor neuron degenerative diseases, Hallervorden-Spatz syndrome, cerebral infarct, cerebral trauma, chronic traumatic encephalopathy, and transient ischemic attack, or any combination thereof. 
     
     
         41 . The method of  claim 40 , wherein the neurodegenerative disease is selected from Alzheimer's disease, frontotemporal dementia, FTLD-U, amyotrophic lateral sclerosis (ALS), and Huntington's chorea. 
     
     
         42 . The method of  claim 37 , wherein viral infection is caused by a virus selected from the group consisting of West Nile virus, Respiratory Syncitial Virus (RSV), herpes simplex virus 1, herpes simplex virus 2, Epstein-Barr virus (EBV), hepatitis virus A, hepatitis virus B, hepatitis virus C, influenza viruses, chicken pox, avian flu viruses, smallpox, polio viruses, HIV-1, and HIV-2, or any combinations thereof. 
     
     
         43 . The method of  claim 37 , wherein the subject is a mammal. 
     
     
         44 . The method of  claim 37 , wherein the subject is a human. 
     
     
         45 . The method of  claim 37 , further comprising the step of diagnosing the subject for said neurodegenerative disease or said viral infection prior to the onset of administration. 
     
     
         46 . The method of  claim 37 , wherein the pathology of said neurodegenerative disease or said viral infection comprises stress granules. 
     
     
         47 . The method of  claim 37 , wherein the pathology of said neurodegenerative disease or said viral infection comprises stress granules or TDP-43 inclusion formation. 
     
     
         48 . A compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         49 . The compound of  claim 48 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         50 . The compound of  claim 48 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         51 . A pharmaceutical composition comprising a compound of  claim 48  or a pharmaceutically acceptable salt thereof.