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Cell Therapeutics in Parkinson's Disease.

Lindvall, Olle LU and Björklund, Anders LU orcid (2011) In Neurotherapeutics 8. p.539-548
Abstract
The main pathology underlying motor symptoms in Parkinson's disease (PD) is a rather selective degeneration of nigrostriatal dopamine (DA) neurons. Intrastriatal transplantation of immature DA neurons, which replace those neurons that have died, leads to functional restoration in animal models of PD. Here we describe how far the clinical translation of the DA neuron replacement strategy has advanced. We briefly summarize the lessons learned from the early clinical trials with grafts of human fetal mesencephalic tissue, and discuss recent findings suggesting susceptibility of these grafts to the disease process long-term after implantation. Mechanisms underlying graft-induced dyskinesias, which constitute the only significant adverse event... (More)
The main pathology underlying motor symptoms in Parkinson's disease (PD) is a rather selective degeneration of nigrostriatal dopamine (DA) neurons. Intrastriatal transplantation of immature DA neurons, which replace those neurons that have died, leads to functional restoration in animal models of PD. Here we describe how far the clinical translation of the DA neuron replacement strategy has advanced. We briefly summarize the lessons learned from the early clinical trials with grafts of human fetal mesencephalic tissue, and discuss recent findings suggesting susceptibility of these grafts to the disease process long-term after implantation. Mechanisms underlying graft-induced dyskinesias, which constitute the only significant adverse event observed after neural transplantation, and how they should be prevented and treated are described. We summarize the attempts to generate DA neurons from stem cells of various sources and patient-specific DA neurons from fully differentiated somatic cells, with particular emphasis on the requirements of these cells to be useful in the clinical setting. The rationale for the new clinical trial with transplantation of fetal mesencephalic tissue is described. Finally, we discuss the scientific and clinical advancements that will be necessary to develop a competitive cell therapy for PD patients. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurotherapeutics
volume
8
pages
539 - 548
publisher
Springer
external identifiers
  • wos:000296733700002
  • pmid:21901584
  • scopus:80955142155
  • pmid:21901584
ISSN
1878-7479
DOI
10.1007/s13311-011-0069-6
language
English
LU publication?
yes
id
dd2fd672-b1b6-4854-9c6e-ec19dea7bc9d (old id 2169058)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21901584?dopt=Abstract
date added to LUP
2016-04-04 08:48:49
date last changed
2022-04-23 18:04:35
@article{dd2fd672-b1b6-4854-9c6e-ec19dea7bc9d,
  abstract     = {{The main pathology underlying motor symptoms in Parkinson's disease (PD) is a rather selective degeneration of nigrostriatal dopamine (DA) neurons. Intrastriatal transplantation of immature DA neurons, which replace those neurons that have died, leads to functional restoration in animal models of PD. Here we describe how far the clinical translation of the DA neuron replacement strategy has advanced. We briefly summarize the lessons learned from the early clinical trials with grafts of human fetal mesencephalic tissue, and discuss recent findings suggesting susceptibility of these grafts to the disease process long-term after implantation. Mechanisms underlying graft-induced dyskinesias, which constitute the only significant adverse event observed after neural transplantation, and how they should be prevented and treated are described. We summarize the attempts to generate DA neurons from stem cells of various sources and patient-specific DA neurons from fully differentiated somatic cells, with particular emphasis on the requirements of these cells to be useful in the clinical setting. The rationale for the new clinical trial with transplantation of fetal mesencephalic tissue is described. Finally, we discuss the scientific and clinical advancements that will be necessary to develop a competitive cell therapy for PD patients.}},
  author       = {{Lindvall, Olle and Björklund, Anders}},
  issn         = {{1878-7479}},
  language     = {{eng}},
  pages        = {{539--548}},
  publisher    = {{Springer}},
  series       = {{Neurotherapeutics}},
  title        = {{Cell Therapeutics in Parkinson's Disease.}},
  url          = {{http://dx.doi.org/10.1007/s13311-011-0069-6}},
  doi          = {{10.1007/s13311-011-0069-6}},
  volume       = {{8}},
  year         = {{2011}},
}