Cell transplants have long been proposed as a possible therapy for Parkinson disease, but a series of reports in Nature Medicine suggest that the pathology may spread from the host to the transplants.
Parkinson disease results from the abnormal aggregation of a protein known as alpha-synuclein and the degeneration of the substantia nigra, a dopamine-releasing region of the midbrain. Therapies for the disease aiming at replacing the lost cells have given hope and, in the 1990s, clinical trials transplanting dopaminergic fetal brain tissue into the brains of patients with Parkinson took place. Two independent groups led by Patrik Brundin and by Jeffrey Kordower report that the transplanted tissue in some subjects shows evidence of alpha-synuclein aggregates. This observation is striking because the grafts were too young to develop this on their own, and the fetal tissue had been placed into the striatum, a brain region that receives input from the substantia nigra but does not develop alpha-synuclein aggregates in Parkinson disease. So, in these subjects, the disease seems to have spread from the host to the graft. But not all studies agree. A third study, led by Ole Isacson, failed to show Parkinson-like pathology in the transplants from a different set of similar subjects, finding instead a large proportion of serotonergic, and not only dopaminergic, neurons within the grafts. As current efforts to develop cell-replacement therapies focus on the use of stem cells to generate substantia nigra-like dopaminergic neurons, the findings of these three groups on long-term transplant recipients add a level of complexity to the idea of curing Parkinson disease with grafted tissue. Author contacts: Patrik Brundin (Wallenberg Neuroscience Center, Lund, Sweden)
E-mail: patrik.brundin@med.lu.se Jeffrey Kordower (Rush University Medical Center, Chicago, IL, USA)
E-mail: jkordowe@rush.edu Ole Isacson (Harvard Medical School/McLean Hospital, Belmont, MA, USA)
E-mail: isacson@hms.harvard.edu Abstracts available online: Abstract of Paper 1.
Abstract of Paper 2.
Abstract of Paper 3. (C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza
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