Parkinson's disease is a relentlessly progressive neurodegenerative disorder afflicting over 500,000 Americans. Patients with parkinsonism can expect to live a normal lifespan due to levodopa and other drug therapies, but most experience a steadily eroding quality of life in the later stages of the disease. This program project was organized to (i) systematically investigative adrenal chromaffin cell transplantation as an approach to treating Parkinson's disease, and (ii) better understand the mechanisms underlying functional recovery from parkinsonism in rodent and nonhuman primate models of Parkinson's disease. The present program consists of three projects and two core facilities. In Project 1, Dr. Gash will critically test the hypothesis that increasing chromaffin cell survival in intrastriatal grafts significantly increases behavioral recovery in parkinsonian primates. In Project 2, Dr. Notter will characterize in depth the properties of primate Schwann cells and chromaffin cells by bioassays, immunoblasts and in situ hybridization for mRNA. She will also evaluate the response of primate chromaffin cells to factors they will be exposed to in implant sites including a aFGF, cytokines, macrophage-derived factors and levodopa. Dr. Hansen, in Project 3, using a selective lesion rat model will test the hypothesis that a host sprouting response is important for restoring striatal dopamine levels and may be the single most important event in ameliorating functional deficits that result from dopamine depletion in the striatum. Collectively, these studies should not only increase our understanding of the processes important for functional recovery from parkinsonism but should also be of significant benefit in designing new therapeutic approaches to the treatment of Parkinson's disease.
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