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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Barker, Roger A 
TRANSEURO consortium 

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 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.

Description

Keywords

Clinical Trials as Topic, Dopaminergic Neurons, Fetal Tissue Transplantation, Humans, Immunosuppressive Agents, Parkinson Disease, Research Design, Stem Cell Transplantation

Journal Title

Nat Med

Conference Name

Journal ISSN

1078-8956
1546-170X

Volume Title

25

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
European Commission (242003)
Cure Parkinson's Trust (Transeuro Follow Up Study)
Cure Parkinson's Trust (RVG9R- p137)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0616-10011)
Medical Research Council (MC_PC_12009)
Wellcome Trust (203151/Z/16/Z)
This study was supported by an EU FP7 grant (242003) as well as funding from the Cure Parkinson’s Trust (RG81537), John Black Charitable Trust and Multipark. The work was also supported by NIHR funding of Biomedical Research Centres at UCL and Cambridge (146281). RAB is an NIHR Senior Investigator (NF-SI-0616-10011) and a PI in the MRC/WT Stem Cell Institute (203151/Z/16/Z).