Subthalamic GAD gene therapy in a Parkinson's disease rat model.

Publication Type	Academic Article
Authors	Luo J, Kaplitt M, Fitzsimons H, Zuzga D, Liu Y, Oshinsky M, During M
Journal	Science
Volume	298
Issue	5592
Pagination	425-9
Date Published	10/11/2002
ISSN	1095-9203
Keywords	Genetic Therapy, Glutamate Decarboxylase, Isoenzymes, Neurons, Parkinsonian Disorders, Substantia Nigra, Subthalamic Nucleus
Abstract	The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition of the subthalamic nucleus (STN), and excessive activity of the major output nuclei. Using adeno-associated viral vector-mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), the enzyme that catalyzes synthesis of the neurotransmitter GABA, in excitatory glutamatergic neurons of the STN in rats. The transduced neurons, when driven by electrical stimulation, produced mixed inhibitory responses associated with GABA release. This phenotypic shift resulted in strong neuroprotection of nigral dopamine neurons and rescue of the parkinsonian behavioral phenotype. This strategy suggests that there is plasticity between excitatory and inhibitory neurotransmission in the mammalian brain that could be exploited for therapeutic benefit.
DOI	10.1126/science.1074549
PubMed ID	12376704