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

Dennis D. Spencer, Richard J. Robbins, Frederick Naftolin, Kenneth L. Marek, Timothy Vollmer, Csaba Leranth, Robert h. Roth, Lawrence H. Price, Albert Gjedde, Benjamin S. Bunney, Kimberlee J. Sass, John D. Elsworth, E. Leon Kier, Robert Makuch, Paul B. Hoffer, D. Eugene Redmond

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376 Scopus citations

Abstract

Background. 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. Methods. 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. Results. The procedure was well tolerated. Three ease 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 antiparkinsonian medications, whereas the controls required more medication. Positron-emission tomography with [18F]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. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)1541-1548
Number of pages8
JournalNew England Journal of Medicine
Volume327
Issue number22
DOIs
StatePublished - Nov 26 1992

ASJC Scopus subject areas

  • Medicine(all)

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