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Cell-based therapies for Parkinson disease-past insights and future potential.

Barker, Roger LU ; Drouin-Ouellet, Janelle LU and Parmar, Malin LU (2015) In Nature Reviews Neurology 11(9). p.492-503
Abstract
Parkinson disease (PD) is characterized by loss of the A9 nigral neurons that provide dopaminergic innervation to the striatum. This discovery led to the successful instigation of dopaminergic drug treatments in the 1960s, although these drugs were soon recognized to lose some of their efficacy and generate their own adverse effects over time. Despite the fact that PD is now known to have extensive non-nigral pathology with a wide range of clinical features, dopaminergic drug therapies are still the mainstay of therapy, and work well for many years. Given the success of pharmacological dopamine replacement, pursuit of cell-based dopamine replacement strategies seemed to be the next logical step, and studies were initiated over 30 years ago... (More)
Parkinson disease (PD) is characterized by loss of the A9 nigral neurons that provide dopaminergic innervation to the striatum. This discovery led to the successful instigation of dopaminergic drug treatments in the 1960s, although these drugs were soon recognized to lose some of their efficacy and generate their own adverse effects over time. Despite the fact that PD is now known to have extensive non-nigral pathology with a wide range of clinical features, dopaminergic drug therapies are still the mainstay of therapy, and work well for many years. Given the success of pharmacological dopamine replacement, pursuit of cell-based dopamine replacement strategies seemed to be the next logical step, and studies were initiated over 30 years ago to explore the possibility of dopaminergic cell transplantation. In this Review, we outline the history of this therapeutic approach to PD and highlight the lessons that we have learned en route. We discuss how the best clinical outcomes have been obtained with fetal ventral mesencephalic allografts, while acknowledging inconsistencies in the results owing to problems in trial design, patient selection, tissue preparation, and immunotherapy used post-grafting. We conclude by discussing the challenges of bringing the new generation of stem cell-derived dopamine cells to the clinic. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Reviews Neurology
volume
11
issue
9
pages
492 - 503
publisher
Nature Publishing Group
external identifiers
  • pmid:26240036
  • wos:000360967300004
  • scopus:84941022742
ISSN
1759-4766
DOI
10.1038/nrneurol.2015.123
language
English
LU publication?
yes
id
f63c0472-9e67-4736-937a-851fbfcc2231 (old id 7844742)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26240036?dopt=Abstract
date added to LUP
2015-09-05 13:38:50
date last changed
2017-11-05 03:06:06
@article{f63c0472-9e67-4736-937a-851fbfcc2231,
  abstract     = {Parkinson disease (PD) is characterized by loss of the A9 nigral neurons that provide dopaminergic innervation to the striatum. This discovery led to the successful instigation of dopaminergic drug treatments in the 1960s, although these drugs were soon recognized to lose some of their efficacy and generate their own adverse effects over time. Despite the fact that PD is now known to have extensive non-nigral pathology with a wide range of clinical features, dopaminergic drug therapies are still the mainstay of therapy, and work well for many years. Given the success of pharmacological dopamine replacement, pursuit of cell-based dopamine replacement strategies seemed to be the next logical step, and studies were initiated over 30 years ago to explore the possibility of dopaminergic cell transplantation. In this Review, we outline the history of this therapeutic approach to PD and highlight the lessons that we have learned en route. We discuss how the best clinical outcomes have been obtained with fetal ventral mesencephalic allografts, while acknowledging inconsistencies in the results owing to problems in trial design, patient selection, tissue preparation, and immunotherapy used post-grafting. We conclude by discussing the challenges of bringing the new generation of stem cell-derived dopamine cells to the clinic.},
  author       = {Barker, Roger and Drouin-Ouellet, Janelle and Parmar, Malin},
  issn         = {1759-4766},
  language     = {eng},
  number       = {9},
  pages        = {492--503},
  publisher    = {Nature Publishing Group},
  series       = {Nature Reviews Neurology},
  title        = {Cell-based therapies for Parkinson disease-past insights and future potential.},
  url          = {http://dx.doi.org/10.1038/nrneurol.2015.123},
  volume       = {11},
  year         = {2015},
}