Ten years after a fetal cell transplant, a Parkinson's patient's graft is still delivering dopamine to postsynaptic cells, according to a study appearing in the December issue of Nature Neuroscience. This unprecedented in vivo confirmation of the graft's viability was achieved by Paola Piccini and her colleagues at the Imperial College School of Medicine in London, in collaboration with the Swedish team, led by Olle Lindvall, that had performed the transplants.
Previous in vivo imaging studies of such patients have demonstrated that human embryonic mesencephalic cells transplanted to the putamen remain alive and produce dopamine. However, it had not been confirmed that they had made functional connections and that dopamine was being delivered with specificity to postsynaptic sites.
Piccini and her colleagues took advantage of the built-in control provided by a patient who had received only a unilateral transplant of fetal cells, which was sufficient to bring about significant clinical improvement. The researchers used PET scans to confirm that endogenous dopamine release had been restored to normal levels on the grafted side of the brain, while it had deteriorated significantly on the nongrafted side. They were further able to demonstrate that the dopamine was not simply floating away from the axon terminals to affect other cells in a nonregulated way, but was binding to postsynaptic D receptors.
This confirmation that brain grafts can innervate host tissue in an apparently normal fashion is especially timely, as an American double-blind, placebo-controlled trial of human fetal dopamine cell transplants has not turned up significant clinical benefit for any but the youngest patients (Freed CR et al. Soc Neurosci Abs 1999;25:212.) In an accompanying News and Views, Roger Barker and Stephen Dunnett suggest that the Swedish technique may be superior to the American one.—Hakon Heimer
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- Piccini P, Brooks DJ, Björklund A, Gunn RN, Grasby PM, Rimoldi O, Brundin P, Hagell P, Rehncrona S, Widner H, Lindvall O. Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci. 1999 Dec;2(12):1137-40. PubMed.
- Barker RA, Dunnett SB. Functional integration of neural grafts in Parkinson's disease. Nat Neurosci. 1999 Dec;2(12):1047-8. PubMed.