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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease

Barker, Roger A. LU ; Farrell, Krista ; Guzman, Natalie Valle ; He, Xiaoling ; Lazic, Stanley E. ; Moore, Sarah ; Morris, Robert ; Tyers, Pamela ; Wijeyekoon, Ruwani and Daft, Danielle , et al. (2019) In Nature Medicine 25. p.1045-1053
Abstract

Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who... (More)

Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.

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publication status
published
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Nature Medicine
volume
25
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:31263283
  • scopus:85068569611
ISSN
1078-8956
DOI
10.1038/s41591-019-0507-2
language
English
LU publication?
yes
id
62107381-c429-4d1d-b197-64842ca5393c
date added to LUP
2019-07-19 09:30:26
date last changed
2021-04-20 02:47:08
@article{62107381-c429-4d1d-b197-64842ca5393c,
  abstract     = {<p>Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.</p>},
  author       = {Barker, Roger A. and Farrell, Krista and Guzman, Natalie Valle and He, Xiaoling and Lazic, Stanley E. and Moore, Sarah and Morris, Robert and Tyers, Pamela and Wijeyekoon, Ruwani and Daft, Danielle and Hewitt, Sam and Dayal, Viswas and Foltynie, Thomas and Kefalopoulou, Zinovia and Mahlknecht, Philipp and Lao-Kaim, Nick P. and Piccini, Paola and Bjartmarz, Hjalmar and Björklund, Anders and Lindvall, Olle and Nelander-Wahlestedt, Jenny and Parmar, Malin and Paul, Gesine and Widner, Hakan and Church, Alistair and Dunnett, Stephen and Peall, Kathryn and Rosser, Anne and Gurruchaga, Jean Marc and Palfi, Stéphane and Piroth, Tobias and Winkler, Christian},
  issn         = {1078-8956},
  language     = {eng},
  pages        = {1045--1053},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease},
  url          = {http://dx.doi.org/10.1038/s41591-019-0507-2},
  doi          = {10.1038/s41591-019-0507-2},
  volume       = {25},
  year         = {2019},
}