Abstract
Aging and environmental toxins have been identified as risk factors for sporadic Parkinson's disease. In this study, we assess the potential for functional recovery induced by glial cell line-derived neurotrophic factor (GDNF) in a diseased and aged primate brain. Male rhesus monkeys, aged 24 to 30 years, received a single intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which resulted in unilateral parkinsonism. It was followed 1 week later by magnetic resonance imaging-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for GDNF (lenti-GDNF, n = 5) or lacZ (lenti-LacZ, n = 4). Lenti-GDNF treated monkeys had a significant improvement in the clinical rating compared with lenti-LacZ starting at 5 weeks after surgery that persisted until necropsy. The fine motor skills on a timed “pick-up test” slowly improved in the lenti-GDNF treated monkeys while lenti-LacZ animals had extreme difficulties or were unable to complete the task. Positron emission tomography scans performed 12...
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