Methods of treating parkinson's disease using viral vectors

Abstract

Methods of delivering viral vectors, particularly recombinant adeno-associated virus (rAAV) virions, to the central nervous system (CNS) using convection enhanced delivery (CED) are provided. The rAAV virions include a nucleic acid sequence encoding a therapeutic polypeptide. The methods can be used for treating CNS disorders such as for treating Parkinson's Disease.

What is claimed is: 
     
         1 . A method for delivering recombinant AAV virions to a subject, comprising administering via convection-enhanced delivery (CED) said rAAV virions into the CNS of the subject, wherein said rAAV virions comprise a nucleic acid sequence encoding a therapeutic polypeptide. 
     
     
         2 . The method of  claim 1 , wherein the administering is done with an osmotic pump. 
     
     
         3 . The method of  claim 1 , wherein the administering is done with an infusion pump. 
     
     
         4 . The method of  claim 1 , wherein the nucleic acid sequence encodes an aromatic-amino-acid decarboxylase (AADC). 
     
     
         5 . The method of  claim 1  wherein the subject is a human. 
     
     
         6 . The method of  claim 1 , wherein the rAAV virions are administered into the striatum. 
     
     
         7 . A method for delivering recombinant AAV virions to a subject having a CNS disorder, comprising administering via convection-enhanced delivery (CED) said virions into the CNS of the subject, wherein said virions comprise a nucleic acid sequence encoding a therapeutic polypeptide. 
     
     
         8 . The method of  claim 7  wherein the CNS disorder is Parkinson's disease, the rAAV virions are administered into the striatum and wherein the nucleic acid sequence encodes AADC 
     
     
         9 . A method for treating a neurodegenerative disease in a subject, said method comprising:
 (a) providing a preparation comprising recombinant adeno-associated virus (rAAV) virions, wherein said virions comprise a nucleic acid sequence that is expressible in transduced cells to provide a therapeutic effect in the subject; and   (b) delivering the preparation to the CNS of the subject using convection-enhanced delivery (CED), wherein said virions transduce neural cells and the nucleic acid sequence is expressed to provide a therapeutic effect in the subject suitable for treating said neurodegenerative disease.   
     
     
         10 . The method of  claim 9 , wherein the neurodegenerative disease is Parkinson's disease. 
     
     
         11 . The method of  claim 9 , wherein the nucleic acid sequence expressible in transduced cells encodes AADC or functional fragment thereof. 
     
     
         12 . The method of  claim 9 , further comprising administering to the subject at least one additional therapeutic compound. 
     
     
         13 . The method of  claim 12  wherein the at least one additional therapeutic compound is L-dopa. 
     
     
         14 . The method of  claim 13 , further comprising administering L-dopa and, optionally, carbidopa to the subject. 
     
     
         15 . A method of determining levels of dopamine activity in the brain of subject comprising:
 (a) administering a labeled tracer to the subject, wherein binding of the tracer to a cell is indicative of dopamine activity; and   (b) imaging the subject's brain to determine the number of cells which bind the labeled tracer, thereby determining levels of dopamine activity in the subject's brain.   
     
     
         16 . The method of  claim 15 , wherein the labeled tracer is 6-[ 18 F]-fluoro-L-m-tryosine ( 18 F-FMT). 
     
     
         17 . The method of  claim 15 , wherein the imaging is positron emission tomograph (PET) imaging.