FETAL NIGRAL GRAFTS SURVIVE AND MEDIATE CLINICAL BENEFIT IN A PATIENTWITH PARKINSONS-DISEASE

We have previously demonstrated that fetal nigral grafts can survive, reinnervate the striatum, and mediate clinically relevant recovery in a patient with Parkinson's disease (PD).(1) Most previous autopsy case s have failed to identify meaningful numbers of viable grafted cells s uggesting that differences in critical transplant variables determine graft viability.(2-4) The present study evaluated the structural and f unctional correlates of fetal nigral transplantation in a second PD pa tient who received fetal nigral grafts according to our previously pub lished transplant protocol.(5) A 61-year-old woman with severe PD rece ived bilateral fetal nigral grafts to the post-commissural putamen fro m seven donor fetuses (four right side and three left side) aged 6.5-9 weeks postconception. This patient died 19 months after surgery from a cause unrelated to the transplant surgery. Her postoperative clinica l course was characterized by improved motor and activities of daily l iving scores during ''off time,'' reduced ''off time,'' and increased ''on'' time without dyskinesia. Positron emission tomography (PET) sca ns revealed a bilateral and progressive increase in fluorodopa (FD) up take within the grafted putamen. Postmortem examination of the right h emisphere revealed large oval-shaped grafts containing more than 138,0 00 tyrosine-hydroxylase-immunoreactive (TH-ir) neurons. Grafted cells formed a seamless border with the host and provided dense TH-ir innerv ation to 78% of the host postcommissural putamen. Graft-mediated sprou ting of host fibers was not observed. These data provide essential con firmation that, under appropriate transplant conditions, grafted nigra l neurons can survive, reinnervate the host striatum, and provide clin ical benefit to PD patients. These findings also support the concept t hat improved motor function and striatal FD uptake on PET after nigral grafting in PD are the result of the viability of grafted neurons and graft-derived reinnervation of the host striatum.