Dopaminergic Neurons Protected from Degeneration by GDNF Gene Therapy

DL Choi-Lundberg(University of Rochester), Qing Lin(University of Rochester), Yung‐Nien Chang(Research Institute for Genetic and Human Therapy), Ya‐Wen Chiang(Research Institute for Genetic and Human Therapy), Carl Hay(Research Institute for Genetic and Human Therapy), H. Mohajeri(University of Rochester), Beverly L. Davidson(University of Iowa), Martha C. Bohn(University of Rochester)
Science
February 7, 1997
10.1126/science.275.5301.838
Cited by 631Open Access
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Abstract

Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenoviral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneration induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into the striatum. Ad GDNF gene therapy reduced loss of DA neurons approximately threefold 6 weeks after 6-OHDA lesion, as compared with no treatment or injection of Ad lacZ or Ad mGDNF (encoding a biologically inactive deletion mutant GDNF). These results suggest that Ad vector-mediated GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.

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