A solid base of scientific information and preliminary clinical trials suggest that fetal nigral transplantation may provide significant clinical benefit for patients with Parkinson's disease. The present proposal is a multicenter, prospective, randomized, double-blind, controlled trial to test whether intrastriatal grafts of fetal mesencephalon can safely improve and alter clinical progression of disability in patients with PD. We will also determine whether putative benefits associated with fetal nigral grafts are influenced by quantity of tissue implanted. After signaling informed consent, 36 patients who meet entry criteria will be randomized to one of three treatment groups: I) Bilateral fetal nigral transplantation into the post-commissural putamen (I donor per side); II) Bilateral fetal nigral transplantation into the post-commissural putamen (4 donors per side); III) Bilateral cosmetic placebo surgery. Eighteen patients will be recruited from the Movement Disorder Centers at each of Mount Sinai Medical Center in New York and Rush Presbyterian Medical Center in Chicago. All surgery will be performed at the University of South Florida in Tampa. Surgery will be performed in two staged procedures separated by one week. Patients randomized to groups I and II will receive nigral grafts implanted bilaterally into the post-commissural putamen. Tissue will be derived from one or four embryos aged 6.5 to 9 weeks post conception as determined by the randomization schedule. Placebo surgery will consist of a skin incision and a cosmetic burr hole that does not extend through the inner table of the skull and does not expose the dura. We will assess disease status by measures of motor function showing """"""""on"""""""" and """"""""off' states, a quality of life scale, and measures of neurophysiologic and cognitive function. Fluorodopa uptake on positron emission tomography (PET) will be employed as a measure of physiologic function and putative graft viability. We will determine if fetal nigral transplantation provides a safe and clinically significant treatment for PD. We will also test the hypothesis that the quantity of fetal mesencephalic tissue implanted into the post-commissural putamen will correlate with the magnitude of functional recovery.
