AAV-GAD gene for rat models of neuropathic pain and Parkinson's disease.

The introduction of therapeutic genes to neurons by genetic modification has potential as an effective treatment for CNS disorders for all that a successful clinical application has not yet been fully implemented. In this paper, we will discussed the role of AAV vectors with the GAD65 gene for animal models of PD and neuropathic pain. AAV vector is one of the most attractive gene delivery vehicles for direct introduction of therapeutic genes into the CNS in the treatment of neurological diseases. GAD65 is present as a membrane-associated form in synapses and is primarily involved in producing synaptic gamma-aminobutyric acid (GABA) for vesicular release. We constructed rAAV-GAD65 expressing rat GAD65 and demonstrated that rat Parkinsonian symptoms can be significantly improved concomitantly with the production of GAD65. We also demonstrated rAAV-GAD65 as a successful gene delivery vehicle in a chronic pain model by administrating rAAV-GAD65 to DRGs because GABA driven by GAD is a major inhibitory neurotransmitter in the dorsal horn of the spinal cord and also plays an important role in the ventral horn. We believe that AAV vectors can be excellent candidates for gene therapy of neurological diseases.