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- Title
Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.
- Authors
Kordower, J H; Emborg, M E; Bloch, J; Ma, S Y; Chu, Y; Leventhal, L; McBride, J; Chen, E Y; Palfi, S; Roitberg, B Z; Brown, W D; Holden, J E; Pyzalski, R; Taylor, M D; Carvey, P; Ling, Z; Trono, D; Hantraye, P; Déglon, N; Aebischer, P
- Abstract
Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.
- Publication
Science (New York, N.Y.), 2000, Vol 290, Issue 5492, p767
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.290.5492.767