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Strategies for bringing stem cell-derived dopamine neurons to the clinic : A European approach (STEM-PD)

Kirkeby, A. LU ; Parmar, M. LU and Barker, R. A. LU (2017) In Progress in Brain Research 230. p.165-190
Abstract

The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents.... (More)

The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents. However, fetal tissue is associated with several ethical and logistical problems and therefore does not represent a realistic route to the clinical treatment of PD in the future. As a result, alternative cell sources have been explored and the methods for producing authentic midbrain dopaminergic neurons from pluripotent cells have now advanced to a stage which makes it possible to efficiently and reproducibly produce DA progenitors at a much higher purity than can be obtained from human fetal tissue. A stem cell-based therapy for PD therefore has the potential to circumvent many of the problems currently associated with fetal tissue grafting. Here, we describe the challenges faced and the strategies that have been pursued in our European effort to bring a human embryonic stem cell (hESC)-derived dopamine cell product to clinical trial for PD.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Clinical trial, Dopaminergic neurons, Fetal ventral mesencephalic tissue, Good manufacturing practice (GMP), Human embryonic stem cells, Parkinson's disease, TRANSEURO, Ventral midbrain
host publication
Functional Neural Transplantation IV Translation to Clinical Application, Part A
series title
Progress in Brain Research
editor
Dunnett, S.B.; Björklund, A.; and
volume
230
pages
165 - 190
external identifiers
  • scopus:85011592165
  • wos:000414257100008
ISSN
0079-6123
ISBN
978-0-12-811738-5
DOI
10.1016/bs.pbr.2016.11.011
language
English
LU publication?
yes
id
f5f437e8-7c71-4c6e-98b7-14e8d58fdd2f
date added to LUP
2017-02-16 06:55:27
date last changed
2018-12-16 05:04:24
@inbook{f5f437e8-7c71-4c6e-98b7-14e8d58fdd2f,
  abstract     = {<p>The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents. However, fetal tissue is associated with several ethical and logistical problems and therefore does not represent a realistic route to the clinical treatment of PD in the future. As a result, alternative cell sources have been explored and the methods for producing authentic midbrain dopaminergic neurons from pluripotent cells have now advanced to a stage which makes it possible to efficiently and reproducibly produce DA progenitors at a much higher purity than can be obtained from human fetal tissue. A stem cell-based therapy for PD therefore has the potential to circumvent many of the problems currently associated with fetal tissue grafting. Here, we describe the challenges faced and the strategies that have been pursued in our European effort to bring a human embryonic stem cell (hESC)-derived dopamine cell product to clinical trial for PD.</p>},
  author       = {Kirkeby, A. and Parmar, M. and Barker, R. A.},
  editor       = {Dunnett, S.B. and Björklund, A.},
  isbn         = {978-0-12-811738-5},
  issn         = {0079-6123},
  keyword      = {Clinical trial,Dopaminergic neurons,Fetal ventral mesencephalic tissue,Good manufacturing practice (GMP),Human embryonic stem cells,Parkinson's disease,TRANSEURO,Ventral midbrain},
  language     = {eng},
  month        = {02},
  pages        = {165--190},
  series       = {Progress in Brain Research},
  title        = {Strategies for bringing stem cell-derived dopamine neurons to the clinic : A European approach (STEM-PD)},
  url          = {http://dx.doi.org/10.1016/bs.pbr.2016.11.011},
  volume       = {230},
  year         = {2017},
}