Unilateral Transplantation of Human Fetal Mesencephalic Tissue into the Caudate Nucleus of Patients with Parkinson's Disease

Abstract

Parkinson's disease is characterized by the loss of midbrain dopamine neurons that innervate the caudate and the putamen. Studies in animals suggest that fetal dopaminergic neurons can survive transplantation and restore neurologic function. This report compares the clinical results in four case patients with severe Parkinson's disease who underwent stereotaxic implantation of human fetal ventral mesencephalic tissue in one caudate nucleus with the results in a control group of similar subjects assigned at random to a one-year delay in surgery. Each case patient received cryopreserved tissue from one fetal cadaver (gestational age, 7 to 11 weeks). Before implantation, adjacent midbrain tissue underwent microbiologic, biochemical, and viability testing. Cyclosporine was administered for six months postoperatively. The procedure was well tolerated. Three case patients showed bilateral improvement on motor tasks, as assessed on videotape, and were more functional in the activities of daily living, as assessed by themselves and neurologists, during both optimal drug therapy and “drug holiday” periods. One case patient, who died after four months from continued disease progression, had striatonigral degeneration at autopsy. In the patients who received transplants, optimal control was achieved with a lower dose of anti-parkinsonism medications, whereas the controls required more medication. Positron-emission tomography with [ 18 F]fluorodopa before and after surgery in one patient revealed a bilateral restoration of caudate dopamine synthesis to the range of normal controls, but continued bilateral deficits in the putamen. Although the case patients continued to be disabled by their disease, unilateral intracaudate grafts of fetal tissue containing dopamine diminished the symptoms and signs of parkinsonism during 18 months of evaluation. (N Engl J Med 1992;327:1541–8.), PARKINSON'S disease is a neurodegenerative disorder characterized histopathologically by the loss of dopaminergic neurons in the substantia nigra that project to striatal neurons in the caudate nucleus and putamen. The resulting decrease in striatal dopamine appears to be a major factor in the characteristic motor and cognitive deficits associated with the disease. Early in the course of the disease a dramatic restoration of neurologic function occurs in response to the dopamine precursor levodopa and dopamine-receptor agonists. As the disease progresses, the response to drugs is often diminished, possibly because of the continued loss of striatal dopaminergic nerve terminals and necessary… © 1992, Massachusetts Medical Society. All rights reserved.