GLUTAMIC ACID DECARBOXYLASE (GAD) BASED DELIVERY SYSTEM
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.