In the past decade neural transplants have been demonstrated to be effective in ameliorating neurological deficits in rodent model systems of Parkinson's disease, Huntington's disease, neuroendocrine disorders and cognitive deficits. This success with transplants in rodents has led to suggestions that neural grafts might be of therapeutic value in treating human neurological disorders including Parkinson's disease. The purpose of the present program project is to address the pre-clinical issue which must be resolved in order to develop a rational clinical approach for using neural transplants to treat Parkinsonism. Our studies begin with the premise that practical sources of donor tissue must be identified if clinical trials are to proceed. Project 1 focuses on the characterization in vitro of potential nonfetal donor tissues including cell lines which might be used for transplantation . An important component of this project is to create cell hybrids of dopaminergic neurons which can be used for implantation. Project 2 conducts the in vivo analysis of the prospective donor tissues identified in Project 1 utilizing rodent model systems of Parkinsonism. Project 3 is also committed to the in vivo analysis of donor tissues in rodent model systems but will concentrate on paraneural tissues and will conduct correlative ultrastructural studies for both Projects 1 and 2. Project 4 will assess the development of MPTP induced Parkinsonism in nonhuman primates and the efficacy of transplants in reversing the functional deficits. Core A is the Laboratory Animal Medical Facility which will be responsible for all nonhuman primates used in these studies. Collectively these projects represent a systematic investigation of potential donor tissues from neonfetal sources which can be utilized clinically for the treatment of Parkinson's disease. The results from these studies should provide the necessary pre-clinical data needed to proceed with clinical investigations.
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