22 November 1999. 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.
Reference:Piccini Brooks DJ, Bjorklund 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;2(12):1137-40. Abstract
Barker and Dunnett. Functional integration of
neural grafts in Parkinson's disease. Nat Neurosci 1999;2(12):1047-8. Abstract