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Science 27 October 2000:
Vol. 290. no. 5492, pp. 767 - 773
DOI: 10.1126/science.290.5492.767
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Research Articles

Neurodegeneration Prevented by Lentiviral Vector Delivery of GDNF in Primate Models of Parkinson's Disease

Jeffrey H. Kordower,1* Marina E. Emborg,1 Jocelyne Bloch,2 Shuang Y. Ma,1 Yaping Chu,1 Liza Leventhal,1 Jodi McBride,1 Er-Yun Chen,1 Stéphane Palfi,1 Ben Zion Roitberg,1 W. Douglas Brown,4 James E. Holden,34 Robert Pyzalski,4 Michael D. Taylor,3 Paul Carvey,5 ZaoDung Ling,5 Didier Trono,6 Philippe Hantraye,7 Nicole Déglon,2 Patrick Aebischer28

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.

1 Department of Neurological Sciences and
5 Department of Pharmacology, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
2 Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland.
3 Department of Medical Physics and
4 Department of Radiology, University of Wisconsin, Madison, WI 53706, USA.
6 Department of Genetics and Microbiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
7 Commissariat a l'Energie Atomique (CEA), CNRS, Unite de Recherche Associe (URA), 2210 Service Hospitalier Frederic Joliot, CEA, Direction des Sciences du Vivant (DSV), Departement de Recherche Medicale (DRM), Orsay cedex, France.
8 Swiss Federal Institute of Technology, EPFL, Lausanne, Switzerland.
*   To whom correspondence should be addressed. E-mail: jkordowe{at}rush.edu

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