Glutamic acid decarboxylase (gad) based delivery system

Abstract

The invention provide methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain that is overstimulated in neurodegenerative diseases. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding glutamic acid decarboxylase (GAD) to cells in the hippocampus, subthalamic nucleus of the basal ganglia, mesaphilia and thalamus.

1 . A method of ameliorating a symptom of a neurodegenerative disorder by altering expression of glutamic acid decarboxylase 67 (GAD 67 ) in a region of the brain of a subject having a neurodegenerative disorder comprising;
 identifying a target site in the brain that requires modification;   delivering an adeno-associated viral (AAV) vector comprising a nucleotide sequence encoding glutamic acid decarboxylase 67 (GAD 67 ) directly to the target site in the brain; and   expressing GAD 67  in the target site, thereby ameliorating at least one symptom of the neurodegenerative disorder.   
     
     
         2 . The method of  claim 1 , wherein the AAV vector is delivered using stereotaxic delivery. 
     
     
         3 . The method of  claim 1 , wherein the region of the brain is selected from the group consisting of basal ganglia, subthalamic nucleus (STN), pedunculopontine nucleus (PPN), substantia nigra (SN), thalamus, hippocampus, cortex, and combinations thereof. 
     
     
         4 . The method of  claim 1 , wherein the region of brain is the subthalamic nucleus (STN). 
     
     
         5 . The method of  claim 1 , wherein the neurodegenerative disorder is Parkinson's disease. 
     
     
         6 . A method of ameliorating a symptom of a neurodegenerative disorder by altering expression of glutamic acid decarboxylase 67 (GAD 67 ) in a region of the brain of a subject having a neurodegenerative disorder which causes morphological and/or functional abnormality of a neural cell or population of neural cells comprising:
 identifying a target site in the brain that requires modification;   delivering an AAV vector comprising a nucleotide sequence encoding glutamic acid decarboxylase 67 (GAD 67 ) directly to the target site in the brain; and   expressing GAD 67  in the target site, thereby ameliorating at least one symptom of the neurodegenerative disorder.   
     
     
         7 . The method of  claim 6 , wherein the AAV vector is delivered using stereotaxic delivery. 
     
     
         8 . The method of  claim 6 , wherein the region of the brain is selected from the group consisting of basal ganglia, subthalamic nucleus (STN), pedunculopontine nucleus (PPN), substantia nigra (SN), thalamus, hippocampus, cortex, and combinations thereof.