Method of treating neurodegenerative disease

Abstract

Aspects featured in the invention relate to compositions and methods for inhibiting alpha-synuclein (SNCA) gene expression, such as for the treatment of neurodegenerative disorders. An anti-SNCA agent featured herein that targets the SNCA gene can have been modified to alter distribution in favor of neural cells.

1 . A method of reducing gene expression in α-synuclein (SNCA) gene in a subject with an antisense or an RNAi agent. 
     
     
         2 . The method of  claim 1 , wherein the SNCA gene is a wild type SNCA gene. 
     
     
         3 . The method of  claim 1 , wherein the subject comprises haplotypes. 
     
     
         4 . The method of  claim 4 , wherein the haplotypes are defined by SNCA REP1 promoter variants. 
     
     
         5 . The method of  claim 1 , wherein the gene expression occurs through ubiquitin carboxy-terminal hydrolase L1 gene or the ubiquitin proteasomal system. 
     
     
         6 . The method of  claim 1 , wherein the subject comprises pre-symptomatic Parkinson's Disease (PD). 
     
     
         7 . The method of  claim 7 , wherein the pre-symptomatic PD is identified by profiling risk factors and studying functional neuroimaging of the subject. 
     
     
         8 . The method of  claim 8 , wherein the functional imaging is selected from the group consisting of fluorodopa and positron emission tomography. 
     
     
         9 . The method of  claim 1 , wherein the RNAi agent is delivered across the blood brain barrier. 
     
     
         10 . The method of  claim 1 , wherein the RNAi agent is administered to a subject orally, parentally, or intraparentchymally. 
     
     
         11 . A method of reducing gene expression in α-synuclein (SNCA) gene in a patient with parkinsonism and/or Lewy body dementia with an antisense or an RNAi agent. 
     
     
         12 . A method of slowing the rate of PD progression by reducing gene expression in α-synuclein (SNCA) gene in a subject with an antisense or an RNAi agent.