Kordower, J HEmborg, M EBloch, JMa, S YChu, YLeventhal, LMcBride, JChen, E YPalfi, SRoitberg, B ZBrown, W DHolden, J EPyzalski, RTaylor, M DCarvey, PLing, ZTrono, DidierHantraye, PDéglon, NAebischer, P2005-09-052005-09-052005-09-05200010.1126/science.290.5492.767https://infoscience.epfl.ch/handle/20.500.14299/215859WOS:0000900676000383066Lentiviral 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.Gene TherapyNerve Growth Factorstext::journal::journal article::research article