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Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson's Patients with Neural Transplants

Politis, Marios; Wu, Kit; Loane, Clare; Quinn, Niall P.; Brooks, David J.; Rehncrona, Stig LU ; Björklund, Anders LU ; Lindvall, Olle LU and Piccini, Paola (2010) In Science Translational Medicine 2(38).
Abstract
Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by L-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated... (More)
Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by L-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT1A) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Translational Medicine
volume
2
issue
38
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • wos:000288428900005
  • scopus:77955617871
ISSN
1946-6242
DOI
10.1126/scitranslmed.3000976
language
English
LU publication?
yes
id
03d58ad7-ce2d-4046-b59a-d0f97d5ce1e7 (old id 1859338)
date added to LUP
2011-04-04 07:19:04
date last changed
2018-07-08 03:06:49
@article{03d58ad7-ce2d-4046-b59a-d0f97d5ce1e7,
  abstract     = {Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by L-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT1A) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.},
  author       = {Politis, Marios and Wu, Kit and Loane, Clare and Quinn, Niall P. and Brooks, David J. and Rehncrona, Stig and Björklund, Anders and Lindvall, Olle and Piccini, Paola},
  issn         = {1946-6242},
  language     = {eng},
  number       = {38},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Translational Medicine},
  title        = {Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson's Patients with Neural Transplants},
  url          = {http://dx.doi.org/10.1126/scitranslmed.3000976},
  volume       = {2},
  year         = {2010},
}