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Robert A. Hauser, MD; Thomas B. Freeman, MD; Barry J. Snow, MD; Michael Nauert, MD; Lisa Gauger, BA; Jeffrey H. Kordower, PhD; C. Warren Olanow, MD

Arch Neurol. 1999;56:179-187.

Background  Parkinson disease (PD) is associated with a progressive loss of nigrostriatal dopamine neurons. Medication therapy provides adequate control of symptoms for several years, but long-term treatment is complicated by progressive disability and the development of motor fluctuations and dyskinesias. In animal models of PD, fetal nigral transplants have been shown to survive grafting into the striatum, provide extensive striatal reinnervation, and improve motor function. In patients with PD, cell survival and clinical benefit have been observed following fetal nigral grafting, but results have been inconsistent.

Objective  To evaluate the safety and efficacy of bilateral fetal nigral transplantation into the postcommissural putamen in patients with advanced PD complicated by motor fluctuations and dyskinesias.

Patients and Methods  Six patients with advanced PD underwent bilateral fetal nigral transplantation. Each patient received solid grafts derived from donors aged 6 to 9 weeks after conception stereotactically implanted into the postcommissural putamen using 3 to 4 donors per side. Cyclosporine was administered for approximately 6 months to provide immune suppression. Clinical evaluations included the Unified Parkinson's Disease Rating Scale (UPDRS), Schwab-England Activities of Daily Living Scale, and timed tests of motor function conducted during both the "off" and "on" states at baseline and at 1, 3, 6, 9, 12, 18, and 24 months following transplantation. Percentage of time off and percentage of time on with and without dyskinesia were recorded at half-hour intervals using home diaries during the week prior to each evaluation. ¹⁸F-fluorodopa positron emission tomographic scans were performed at baseline, and at 6 months and 1 year following transplantation.

Results  Patients have been followed up for a mean ± SD of 20.5 ± 5.5 months. Complications related to surgery were mild and transient. Activities of daily living, motor, and total (activities of daily living plus motor) UPDRS scores during the off state improved significantly (P<.05, Wilcoxon signed rank test) at final visit in comparison with baseline. Mean total UPDRS off score improved 32%, and each patient experienced at least a 19% improvement. Mean percentage of time on without dyskinesia during the waking day improved from 22% to 60% (P<.05). Mean putamenal fluorodopa uptake on positron emission tomography increased significantly at 6 and 12 months in comparison with baseline (P<.001, 2-tailed t test). This increase correlated with clinical improvement. Two patients died 18 months after transplantation from causes unrelated to the surgical procedure. In both cases, histopathological examination showed robust survival of tyrosine hydroxylase immunoreactive cells and abundant reinnervation of the postcommissural putamen.

Conclusions  Fetal nigral tissue can be transplanted into the postcommissural putamen bilaterally in patients with advanced PD safely and with little morbidity. In this open-label pilot study we observed consistent long-term clinical benefit and increased fluorodopa uptake on positron emission tomography. Clinical improvement appears to be related to the survival and function of transplanted fetal tissue.

From the Departments of Neurology (Dr Hauser and Ms Gauger), Pharmacology and Experimental Therapeutics (Drs Hauser and Freeman), and the Division of Neurosurgery (Dr Freeman), University of South Florida, Tampa; the Division of Neurology, University of British Columbia, University Hospital, Vancouver (Dr Snow); Women's Center, Tampa Fla (Dr Nauert); the Department of Neurological Sciences, Rush Presbyterian–St Lukes' Medical Center, Chicago Ill (Dr Kordower); and the Department of Neurology, Mount Sinai School of Medicine, New York, NY (Dr Olanow).

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