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Human embryonic stem cell-derived dopaminergic cells for Parkinson's disease: a phase 1/2 open-label trial.

Overview

Authors: G Paul1,2, H Bjartmarz3, A Kirkeby4,5, J Nelander5, R Smith6, S Kayhanian7,8, A Evans7, B Harry7, E Cutting7, S Fazal7, N P Lao-Kaim9, T van Vliet1, S Ullén10, I Grubor3, O Hansson6, P Piccini9, O Lindvall11, A Björklund5, H Widner1, M Parmar5, R A Barker7,8
ORCID iDs: G Paul, H Bjartmarz, A Kirkeby, R Smith, S Fazal, O Hansson, P Piccini, M Parmar, R A Barker
  1. Department of Neurology, Skåne University Hospital, Lund, Sweden
  2. Department of Clinical Sciences and Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden
  3. Department of Neurosurgery, Skåne University Hospital, Lund, Sweden
  4. Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  5. Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden
  6. Clinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden
  7. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
  8. Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK
  9. Department of Brain Sciences, Imperial College London, London, UK
  10. Clinical Studies Sweden - Forum South, Skåne University Hospital, Lund, Sweden
  11. Lund Stem Cell Center and Division of Neurology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
Institutions: Lund University (Sweden); Skåne University Hospital (Sweden); University of Copenhagen (Denmark); Novo Nordisk Foundation Center for Stem Cell Medicine (Denmark); Wellcome/MRC Cambridge Stem Cell Institute (United Kingdom); University of Cambridge (United Kingdom); Imperial College London (United Kingdom)
Journal: Nature medicine, volume 32, issue 9, pages 3449-3457
Dates: received 16 February 2026; accepted 16 June 2026; published online 9 July 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41591-026-04525-0 · PMID 42426223 · PMCID PMC13577911 · OpenAlex W7167839097
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: human (organism), Parkinson's (population)
Methods: Statistics
Keywords: Stem-cell research, Parkinson's disease
MeSH: Dopaminergic Neurons*, Human Embryonic Stem Cells*, Parkinson Disease*, Stem Cell Transplantation*, Aged, Female, Humans, Male, Middle Aged (* major topic)
Topic: Pluripotent Stem Cells Research (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: DH | NIHR | Health Services Research Programme (NIHR Health Services Research Programme) (NIHR202312, NIHR203312); Novo Nordisk Fonden (Novo Nordisk Foundation) (NNF21CC0073729 (AK), NNF21CC0073729); Vetenskapsrådet (Swedish Research Council) (2021-00661, 2021-0061,MP)
Citations: cited by 1 paper (Europe PMC); 38 references in the paper

Abstract

Parkinson’s disease (PD) is characterized by progressive loss of nigral dopaminergic neurons, resulting in disabling motor symptoms. Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD. Here we report the 12-month primary safety end point and interim efficacy outcomes from a phase 1/2, open-label, multicenter trial evaluating STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. Eight individuals with moderate PD underwent bilateral intraputaminal transplantation at two escalating doses (n = 4 per cohort), followed by 12 months of immunosuppression. Seven participants completed 12-month follow-up; one participant died from a pulmonary infection. No serious adverse events were attributed to the cell product, no graft-induced dyskinesias were observed and serial magnetic resonance imaging showed no evidence of tumor formation. These findings support the feasibility and favorable safety profile of human pluripotent stem cell-derived dopaminergic progenitor transplantation in this early-phase study, with risks primarily associated with the immunosuppression regimen. Ongoing follow-up to 36 months will further evaluate durability, clinical outcomes and graft function. ClinicalTrials.gov identifier: NCT05635409.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

Code availability

No custom code or algorithm central to the conclusions of this study was developed. Statistical analyses were performed using standard software packages as described in the Methods. Any analysis scripts required to reproduce the reported aggregate analyses are available from the corresponding author on reasonable request, subject to institutional approval.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability

The data that support the findings of this study are available within the Article, Extended Data Tables 1–5 and Extended Data Figs. 1 and 2, including Source Data. Additional de-identified participant-level data underlying the results reported in this Article may be made available to qualified researchers on reasonable request, subject to applicable ethical approvals, data protection regulations, participant consent and approval by the study sponsor and relevant institutional data governance bodies. As this is a small first-in-human clinical trial of an advanced therapy medicinal product, individual-level data will not be made publicly available owing to the potential risk of participant re-identification. Requests should include a scientifically sound proposal, a statistical analysis plan and evidence of appropriate ethical and data protection approvals where applicable. Requests will be evaluated by the corresponding author, the study sponsor and relevant institutional representatives. Approved requests will require a data transfer or data use agreement specifying permitted analyses, data security requirements, confidentiality obligations and restrictions on onward sharing. Requests should be directed to Gesine Paul, anticipated response time is within 8–12 weeks of receipt of a complete request. De-identified participant-level data will be available 6 months after publication and for 5 years after publication. The study protocol is available in ref. 37 and as Supplementary Note 1. The clinical trial is registered at ClinicalTrials.gov, NCT05635409 (https://clinicaltrials.gov/ct2/show/NCT05635409), and EudraCT 2021-001366-38. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Nature Portfolio

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 21 authors, 2 keywords, 9 MeSH terms, 3 funders, 37 references.

Cite

This paper

Paul, G., Bjartmarz, H., Kirkeby, A., Nelander, J., Smith, R., Kayhanian, S., Evans, A., Harry, B., Cutting, E., Fazal, S., Lao-Kaim, N. P., van Vliet, T., Ullén, S., Grubor, I., Hansson, O., Piccini, P., Lindvall, O., Björklund, A., Widner, H., . . . Barker, R. A. (2026). Human embryonic stem cell-derived dopaminergic cells for Parkinson's disease: a phase 1/2 open-label trial. Nature medicine, 32(9), 3449-3457. https://doi.org/10.1038/s41591-026-04525-0

BibTeX

@article{paul2026human,
author = {Paul, G and Bjartmarz, H and Kirkeby, A and Nelander, J and Smith, R and Kayhanian, S and Evans, A and Harry, B and Cutting, E and Fazal, S and Lao-Kaim, N P and van Vliet, T and Ullén, S and Grubor, I and Hansson, O and Piccini, P and Lindvall, O and Björklund, A and Widner, H and Parmar, M and Barker, R A},
title = {{Human embryonic stem cell-derived dopaminergic cells for Parkinson's disease: a phase 1/2 open-label trial}},
journal = {Nature medicine},
year = {2026},
month = jul,
volume = {32},
number = {9},
pages = {3449--3457},
publisher = {Nature Portfolio},
issn = {1078-8956},
doi = {10.1038/s41591-026-04525-0},
url = {https://doi.org/10.1038/s41591-026-04525-0},
pmid = {42426223},
pmcid = {PMC13577911}
}

RIS

TY - JOUR
AU - Paul, G
AU - Bjartmarz, H
AU - Kirkeby, A
AU - Nelander, J
AU - Smith, R
AU - Kayhanian, S
AU - Evans, A
AU - Harry, B
AU - Cutting, E
AU - Fazal, S
AU - Lao-Kaim, N P
AU - van Vliet, T
AU - Ullén, S
AU - Grubor, I
AU - Hansson, O
AU - Piccini, P
AU - Lindvall, O
AU - Björklund, A
AU - Widner, H
AU - Parmar, M
AU - Barker, R A
TI - Human embryonic stem cell-derived dopaminergic cells for Parkinson's disease: a phase 1/2 open-label trial
T2 - Nature medicine
J2 - Nat Med
PY - 2026
DA - 2026/07/09
VL - 32
IS - 9
SP - 3449
EP - 3457
SN - 1078-8956
PB - Nature Portfolio
DO - 10.1038/s41591-026-04525-0
UR - https://doi.org/10.1038/s41591-026-04525-0
LA - en
ER -

CSL-JSON

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