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Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up

Lindvall, O LU ; Rehncrona, S LU ; Brundin, P LU ; Gustavii, B LU ; Astedt, B; Widner, H LU ; Lindholm, Torun; Björklund, A LU ; Leenders, K L and Rothwell, J C, et al. (1989) In Archives of Neurology 46(6). p.31-615
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... (More)

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.

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@article{0663142b-95f8-4c9e-a215-912a885e6805,
  abstract     = {<p>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.</p>},
  author       = {Lindvall, O and Rehncrona, S and Brundin, P and Gustavii, B and Astedt, B and Widner, H and Lindholm, Torun and Björklund, A and Leenders, K L and Rothwell, J C and Frackowiak, R S and Marsden, C D and Johnels, B and Steg, Pierre G and Freedman, R and Hoffer, B J and Seiger, Ake and Bygdeman, M and Strömberg, I and Olson, L.},
  issn         = {0003-9942},
  keyword      = {Contingent Negative Variation,Corpus Striatum,Dopamine,Female,Fetus,Follow-Up Studies,Humans,Levodopa,Methods,Middle Aged,Movement,Nerve Tissue,Neurologic Examination,Neurons,Neuropsychological Tests,Parkinson Disease,Self Concept,Tomography, Emission-Computed,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {6},
  pages        = {31--615},
  publisher    = {American Medical Association},
  series       = {Archives of Neurology},
  title        = {Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up},
  url          = {http://dx.doi.org/10.1001/archneur.1989.00520420033021},
  volume       = {46},
  year         = {1989},
}