The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease
Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson's disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial ( NCT01898390 ) was designed to determine whether this approach could be further developed into a clinically useful treatment. Owing to poor availability of human fetal ventral mesencephalic tissue, only 11 individuals were grafted at two centers using the same tissue preparation protocol but different implantation devices. No overall clinical effect was seen for the primary endpoint 3 years after grafting. No major graft-induced dyskinesias were seen, but we observed differences in outcome related to transplant device and/or site. Mean dopamine uptake improved at 18 months in seven individuals according to [<sup>18</sup>F]fluorodopa positron emission tomography imaging but was restored to near-normal levels in only one individual. Our findings highlight the need for a stem cell source of dopamine neurons for potential Parkinson's disease cell therapy and provide critical insights into how such clinical studies should be approached.
Authors
- Zinovia Kefalopoulou (ORCID: https://orcid.org/0000-0002-5310-9259)
- Amy Evans
- Sam Hewitt (ORCID: https://orcid.org/0000-0002-9219-6324)
- Ruwani Wijeyekoon
- Gesine Paul (ORCID: https://orcid.org/0000-0002-6806-2254)
- Malin Parmar (ORCID: https://orcid.org/0000-0001-5002-4199)
- Rachel Hills (ORCID: https://orcid.org/0000-0002-4021-4068)
- Olle Lindvall (ORCID: https://orcid.org/0000-0003-0702-8930)
- Victoria H. Roberton (ORCID: https://orcid.org/0000-0002-0404-6984)
- Kathryn J. Peall (ORCID: https://orcid.org/0000-0003-4749-4944)
- Stanley E. Lazic (ORCID: https://orcid.org/0000-0002-3409-3407)
- Debbie Williams
- Mariah J. Lelos (ORCID: https://orcid.org/0000-0001-7102-055X)
- Thomas Foltynie (ORCID: https://orcid.org/0000-0003-0752-1813)
- Paola Piccini (ORCID: https://orcid.org/0000-0003-4162-6141)
- Tagore Nakornchai (ORCID: https://orcid.org/0000-0003-1573-9812)
- Viswas Dayal (ORCID: https://orcid.org/0000-0002-9083-234X)
- Sarah A. Moore (ORCID: https://orcid.org/0000-0003-3712-0199)
- Krista Sibley
- Stephen B. Dunnett (ORCID: https://orcid.org/0000-0003-1826-1578)
- Dilan Athauda (ORCID: https://orcid.org/0000-0001-8594-2483)
- Emma Cutting
- Anders Björklund (ORCID: https://orcid.org/0000-0002-5676-6203)
- Anne Rosser (ORCID: https://orcid.org/0000-0002-4716-4753)
- Adriana Roca‐Fernández (ORCID: https://orcid.org/0000-0002-8720-9397)
- Anne-Marie McGorrian
- Claire Kelly (ORCID: https://orcid.org/0000-0002-0029-9597)
- Naomi Hannaway (ORCID: https://orcid.org/0000-0001-8608-7757)
- Antonio Martín‐Bastida (ORCID: https://orcid.org/0000-0002-8480-7009)
- Caroline Scherf (ORCID: https://orcid.org/0000-0002-0208-6317)
- K.L. Shires
- Andreas–Antonios Roussakis (ORCID: https://orcid.org/0000-0001-5748-6978)
- Alistair Church
- Shane Grealish (ORCID: https://orcid.org/0000-0002-7676-7924)
- Sam Rowlands (ORCID: https://orcid.org/0000-0001-5940-9079)
- Nicholas P Lao–Kaim (ORCID: https://orcid.org/0000-0002-0241-7630)
- Xiaoling He (ORCID: https://orcid.org/0009-0004-1002-8418)
- Danielle Daft
- Harry Bulstrode (ORCID: https://orcid.org/0000-0002-3480-108X)
- Roger A. Barker (ORCID: https://orcid.org/0000-0001-8843-7730)
- Krista Farrell
- Hjálmar Bjartmarz (ORCID: https://orcid.org/0000-0003-3944-8139)
- Philipp Mahlknecht (ORCID: https://orcid.org/0000-0003-0671-0516)
- Jenny Nelander-Wahlestedt
- Robert C. Morris
- Pamela Tyers
- Ngoc Nga Vinh
- Natalie Valle Guzman
- Eduardo M. Torres
- Caroline Williams-Gray
- Håkan Widner
- Linnea Roupé
Institutions
- Lund University (SE)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Hammersmith Hospital (GB)
- Skåne University Hospital (SE)
- University College London (GB)
- Imperial College London (GB)
- Cardiff University (GB)
Publication Details
- Journal
- Nature Biotechnology
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1038/s41587-025-02567-2
- Citations
- 10
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 8.06
Funders
- New York Stem Cell Foundation
- Wellcome
- Van Andel Research Institute
- Cure Parkinson’s Trust
- Wellcome Trust
- UK Research and Innovation
- National Institute for Health and Care Research
- Department of Health and Social Care
- Parkinson's UK
- Imperial College London
- Imperial College Healthcare NHS Trust
- Rosetrees Trust
- Svenska Forskningsrådet Formas
- Lunds Universitet
- Hjärnfonden
- Vetenskapsrådet
- National Institutes of Health
- Parkinsonfonden
- Medical Research Council
- NIHR Imperial Biomedical Research Centre
- NIHR Cambridge Biomedical Research Centre