Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subthalamic GAD Gene Therapy in a Parkinson's Disease Rat Model
Jia Luo,12Michael G. Kaplitt,3Helen L. Fitzsimons,1*David S. Zuzga,2Yuhong Liu,2Michael L. Oshinsky,2Matthew J. During12
The motor abnormalities of Parkinson's disease (PD) are caused by
alterations in basal ganglia network activity, includingdisinhibition
of the subthalamic nucleus (STN), and excessiveactivity of the major
output nuclei. Using adeno-associated viralvector-mediated somatic
cell gene transfer, we expressed glutamicacid decarboxylase (GAD), the
enzyme that catalyzes synthesisof the neurotransmitter GABA, in
excitatory glutamatergic neuronsof the STN in rats. The transduced
neurons, when driven by electricalstimulation, produced mixed
inhibitory responses associated withGABA release. This phenotypic
shift resulted in strong neuroprotectionof nigral dopamine neurons and
rescue of the parkinsonian behavioralphenotype. This strategy suggests
that there is plasticity betweenexcitatory and inhibitory
neurotransmission in the mammalian brainthat could be exploited for
1 Functional Genomics and Translational
Neuroscience Laboratory, Department of Molecular Medicine and
Pathology, University of Auckland, Auckland, New Zealand.
2 CNS Gene Therapy Center, Jefferson Medical
College, Philadelphia, PA 19107, USA.
3 Center for
Stereotactic and Functional Neurosurgery, Department of Neurological
Surgery, Weill Medical College of Cornell University, New York, NY
Present address: Neurologix Inc., Delaware Biotechnology
Institute, 15 Innovation Way, Newark, DE 19711, USA.
To whom correspondence should be addressed. E-mail:
The editors suggest the following Related Resources on Science sites: