Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease |
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| 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 |
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| Institution: | Department of Neurological Sciences, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. jkordowe@rush.edu |
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| 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. |
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