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Human Fetal Dopamine Neurons Grafted Into the Striatum in Two Patients With Severe Parkinson's DiseaseA Detailed Account of Methodology and a 6-Month Follow-up
Olle Lindvall, MD, PhD;
Stig Rehncrona, MD, PhD;
Patrik Brundin, MD, PhD;
Björn Gustavii, MD, PhD;
Birger Åstedt, MD, PhD;
H kan Widner, MD, PhD;
Tore Lindholm, MD, PhD;
Anders Björklund, MD, PhD;
Klaus L. Leenders, MD, PhD;
John C. Rothwell, MD, PhD;
Richard Frackowiak, MD, PhD;
C. David Marsden, MD, PhD;
Bo Johnels, MD, PhD;
Göran Steg, MD, PhD;
Robert Freedman, MD, PhD;
Barry J. Hoffer, MD, PhD;
Åke Seiger, MD, PhD;
Marc Bygdeman, MD, PhD;
Ingrid Strömberg, MD, PhD;
Lars Olson, MD, PhD
Arch Neurol. 1989;46(6):615-631.
Abstract
• By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.
Author Affiliations
From the Departments of Neurology (Drs Lindvall and Widner), Neurosurgery (Dr Rehncrona), Medical Cell Research (Drs Lindvall, Brundin, and Björklund), Gynaecology (Drs Gustavii and Åstedt), and Nephrology (Dr Lindholm), University of Lund (Sweden); the Departments of Clinical Immunology (Dr Widner) and Geriatric Medicine (Dr Seiger), Karolinska Institute, Huddinge, Sweden; the MRC Cyclotron Unit, Hammersmith Hospital (Drs Leenders and Frackowiak) and the University Department of Clinical Neurology, Institute of Neurology, National Hospital (Drs Rothwell and Marsden), London, England; the Department of Neurology, University of Göteborg (Sweden) (Drs Johnels and Steg); the Departments of Psychiatry (Dr Freedman) and Pharmacology (Dr Hoffer), University of Colorado Health Sciences Center, Denver; the Department of Neurological Surgery, University of Miami (Fla) (Dr Seiger); and the Departments of Gynaecology (Dr Bygdeman) and Histology and Neurobiology (Drs Strömberg and Olson), Karolinska Institute, Stockholm, Sweden.
Footnotes
Accepted for publication March 23, 1989.
Reprint requests to Department of Neurology, University Hospital S221 85, Lund, Sweden (Dr Lindvall).
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