The goal of this renewal period will be to study the value of cyclosporine A immunosuppression and basic fibroblast growth factor at improving cell survival and behavioral performance following transplant of fetal mesencephalic dopamine cells in a monkey model of Parkinson's Disease. These studies are a direct extension of the experience of our laboratory in transplanting fetal cells into the MPTP lesioned monkey. Most groups working with transplants in monkeys have found that fetal dopamine cells from early in development (6 to 9 weeks' gestation) can survive in adult brain and produce some behavioral effects. Nonetheless, recovery is not complete, and the survival rate of cells varies considerably between monkeys. The value of immunosuppressant therapy for promoting cell survival and enhancing behavioral improvement is unexplored in monkeys. Basic fibroblast growth factor has been shown in rats to improve fetal mesencephalic dopamine cell survival in tissue culture and in rats to improve fetal neuronal grafts. For these experiments, we will switch from monkeys systemically lesioned with MPTP to monkeys which have been unilaterally lesioned with the neurotoxin MPTP injected into the carotid artery. The reason for this change in MPTP model comes from the difficulty in getting a reproducible and stable Parkinson syndrome of moderate severity in systemically lesioned animals. Transplant success will be evaluated by changes in learned performance in a new motor task we have devised as well as by measurements of spontaneous and apomorphine induced circling.
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