Gene Therapy in a Nonhuman Primate Model of Parkinson's Disease
Abstract
In the third year of this grant, we are about to complete one experiment, and have initiated another. In Experiment 1, we assessed whether lentiviral delivery of the antiapoptotic gene Bcl-2 could prevent the functional and structural consequences of MPTP toxicity in nonhuman primates. Our preliminary data indicate that lentiviral delivery of Bcl2 did not influence MPTP-mediated motor deficits as measured on a clinical rating scale and an operant hand reach task, likely because Bcl-2 may not be able to preserve striatal dopaminergic innervation. We are currently evaluating Neurochemically and morphologically whether lenti- Bcl2 provided neuroprotection at the level of the substantia nigra. We have just initiated a second experiment in which aged monkeys are assessed for levodopa-induced dyskinesias and given a fluorodopa PET scan. They then receive lenti-GDNF under the control of the tetracycline promoter. Three months following lenti-GDNF, they are again assessed for levodopa-induced dyskinesias and given a fluorodopa PET scan. Then half of the aged monkeys receive tetracycline to shut of the GDNF expression in vivo. Monkeys are assessed for levodopa- induced dyskinesias and given a fluorodopa PET scan 3 and 6 months later. This study will determine whether we can control gene expression in vivo and make gene therapy safe for clinical use.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA398254
Entities
People
- Jeffrey H. Kordower
Organizations
- Rush University Medical Center