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Cellular Replacement Therapy for Parkinson's Disease—Where We Are Today?Neural Transplantation and Repair Program, Departments of Psychiatry and Neurosurgery, Yale University School of Medicine The concept of replacing lost dopamine neurons in Parkinson's disease using mesencephalic brain cellsfrom fetal cadavers has been supported by over 20 years of research in animals and over a decade of clinicalstudies. The ambitious goal of these studies was no less than a molecular and cellular "cure" forParkinson's disease, other neurodegenerative diseases, and spinal cord injury. Much research has beendone in rodents, and a few studies have been done in nonhuman primate models. Early uncontrolled clinicalreports were enthusiastic, but the outcome of the first randomized, double blind, controlled study challengedthe idea that dopamine replacement cells can cure Parkinson's disease, although there were somesignificant positive findings. Were the earlier animal studies and clinical reports wrong? Should we give upon the goal? Some aspects of the trial design and implantation methods may have led to lack of effectsand to some side effects such as dyskinesias. But a detailed review of clinical neural transplants publishedto date still suggests that neural transplantation variably reverses some aspects of Parkinson's disease,although differing methods make exact comparisons difficult. While the randomized clinical studies havebeen in progress, new methods have shown promise for increasing transplant survival and distribution,reconstructing the circuits to provide dopamine to the appropriate targets and with normal regulation.Selected promising new strategies are reviewed that block apoptosis induced by tissue dissection, promotevascularization of grafts, reduce oxidant stress, provide key growth factors, and counteract adverse effectsof increased age. New sources of replacement cells and stem cells may provide additional advantages forthe future. Full recovery from parkinsonism appears not only to be possible, but a reliable cell replacementtreatment may finally be near.
Key Words: fetal neural transplantation • Parkinson's • human primate stem cell
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