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7 juni 2026: Bron: Sumitomo Pharma

Het Japanse Ministerie van Volksgezondheid, Arbeid en Welzijn heeft Amchepry, een stamceltherapie voor de ziekte van Parkinson, voorwaardelijk goedgekeurd. Amchepry is ontwikkeld voor patiënten die niet reageren op levodopa en is bedoeld om dopamine producerende hersencellen te vervangen.
Eerdere studies toonden verhoogde dopamine niveaus en motorische verbeteringen met overwegend milde bijwerkingen.

De goedkeuring is gebaseerd op de resultaten van een fase 1/2-studie (jRCT2090220384), waaruit bleek dat getransplanteerde dopaminerge progenitorcellen overleefden en dopamine produceerden in de hersenen. Deze bevindingen suggereren dat de therapie veilig kan zijn en klinisch voordeel kan bieden aan mensen met de ziekte van Parkinson.

Amchepry is een kant-en-klare stamceltherapie gemaakt van geïnduceerde pluripotente stamcellen (iPSC's) verkregen van gezonde donoren. iPSC's worden gecreëerd door volwassen cellen, meestal uit de huid of het bloed, en zijn te herprogrammeren tot een stamceltoestand die kan worden gestuurd om zich te ontwikkelen tot vele verschillende celtypen, waaronder dopamine producerende neuronen. Voor deze therapie worden de iPSC's gestuurd om zich te ontwikkelen tot dopaminerge neuron-voorlopercellen.
Deze cellen worden operatief geïmplanteerd in het striatum, een hersengebied dat betrokken is bij beweging, waar ze kunnen rijpen tot dopamine producerende neuronen. Het doel is om verloren zenuwcellen te vervangen en de dopamine signalering te herstellen.

De door onderzoekers geïnitieerde fase 1/2-studie, uitgevoerd in het Kyoto University Hospital, omvatte zeven patiënten in de leeftijd van 50 tot 69 jaar die een lage of hoge dosis Amchepry kregen.
De studie rapporteerde in totaal 73 bijwerkingen: 72 milde en één matige vorm van dyskinesie.
De meest voorkomende klacht was jeuk op de injectieplaats. Er werden geen ernstige bijwerkingen gemeld die ziekenhuisopname vereisten of tot de dood leidden, en beeldvormend onderzoek toonde geen tekenen van tumorachtige celgroei.
Hersenscans lieten een toename van 44,7% zien in de dopamine concentratie in het striatum, het hersengebied dat beweging controleert. Het effect bleek dosisafhankelijk: de dopamine concentratie steeg met ongeveer 7% in de groep met de lage dosis en met 63,5% in de groep met de hoge dosis.

Uit gegevens over de werkzaamheid van zes patiënten die twee jaar na de transplantatie werden geëvalueerd, bleek dat de motorische functie significant verbeterde. Tijdens de 'off'-periodes, wanneer de werking van de medicatie afneemt, vertoonden de patiënten een gemiddelde afname van 20,4% in de motorische scores van deel III van de MDS Unified Parkinson’s Disease Rating Scale. Tijdens de 'on'-periodes, wanneer de symptomen beter onder controle zijn met medicatie, verbeterden de motorische scores met 35,7%.
Vier patiënten vertoonden tijdens de 'off'-periodes ook een verminderde ziekte ernst, gebaseerd op verbeteringen in hun Hoehn-Yahr-stadium.

De resultaten suggereerden tevens dat een relatief mild immunosuppressief regime voldoende was om afstoting bij de deelnemers aan de studie te voorkomen.

Het volledige studierapport van de fase I/II studie is in Nature gepubliceerd en gratis in te zien. Klik op de titel van het abstract:

Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson’s disease

Nature volume 641, pages971–977 (2025) Cite this article

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Abstract

Parkinson’s disease is caused by the loss of dopamine neurons, causing motor symptoms. Initial cell therapies using fetal tissues showed promise but had complications and ethical concerns1,2,3,4,5. Pluripotent stem (PS) cells emerged as a promising alternative for developing safe and effective treatments6. In this phase I/II trial at Kyoto University Hospital, seven patients (ages 50–69) received bilateral transplantation of dopaminergic progenitors derived from induced PS (iPS) cells. Primary outcomes focused on safety and adverse events, while secondary outcomes assessed motor symptom changes and dopamine production for 24 months. There were no serious adverse events, with 73 mild to moderate events. Patients’ anti-parkinsonian medication doses were maintained unless therapeutic adjustments were required, resulting in increased dyskinesia. Magnetic resonance imaging showed no graft overgrowth. Among six patients subjected to efficacy evaluation, four showed improvements in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III OFF score, and five showed improvements in the ON scores. The average changes of all six patients were 9.5 (20.4%) and 4.3 points (35.7%) for the OFF and ON scores, respectively. Hoehn–Yahr stages improved in four patients. Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) influx rate constant (Ki) values in the putamen increased by 44.7%, with higher increases in the high-dose group. Other measures showed minimal changes.

This trial (jRCT2090220384) demonstrated that allogeneic iPS-cell-derived dopaminergic progenitors survived, produced dopamine and did not form tumours, therefore suggesting safety and potential clinical benefits for Parkinson’s disease.

Statistical analysis

Clinical data were collected by using EDMS-Online (v.3.1, EPS). Safety and efficacy outcomes were summarized using mean values, s.d. values and proportions. Statistical analyses of the clinical data were conducted using SAS software (v.9.4, SAS Institute). Statistical analyses of animal experiments were performed using GraphPad Prism (v.10.3.1, GraphPad Software).

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

Data availability

All relevant data from this trial are included in the Article and Supplementary Methods. Source data are provided with this paper.

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Acknowledgements

We thank all of the patients who participated in this trial; Y. Shimizu, T. Saga and K. Togashi for brain imaging; members of the Efficacy and Safety Evaluation Committee, including S. Kinoshita, H. Sawada and H. Toda for their advice; doctors and coordinators at the Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital, including A. Shimizu, Y. Nagai, M. Yamamoto, R. Uozumi, Y. Kusunoki, A. Kuroda, K. Endo, K. Enomoto, A. Kinoshita, C. Kimura, K. Kawaguchi, C. Ichihara, N. Matsuyama, K. Tochigi, Y. Sameshima, M. Iwasaki and C. Toyooka for supporting this clinical trial; the technical staff of J.T.’s laboratory, including E. Yamasaki, T. Ashida, Y. Fujita, Y. Tanikawa, Y. Katano, Y. Ozaki, R. Takaichi, A. Mihara, K. Fukushima and S. Baba for cell manufacturing; PD project members of Sumitomo Pharma, including K. Yoshida, H. Takahashi, Y. Sugao, S. Sekiya, M. Ikeda, Y. Yamamoto, S. Ota, S. Okabe, H. Ohara and T. Karino for regulatory support and cell manufacturing; and K. Hui for reading this manuscript. This study was supported by a grant from the Research Project for Practical Application of Regenerative Medicine of the Japan Agency for Medical Research and Development (AMED) (23bk0104126h0003) to J.T.

Author information

These authors contributed equally: Nobukatsu Sawamoto, Daisuke Doi, Etsuro Nakanishi, Masanori Sawamura

Authors and Affiliations

Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Nobukatsu Sawamoto, Etsuro Nakanishi, Masanori Sawamura, Hodaka Yamakado, Yosuke Taruno, Atsushi Shima & Ryosuke Takahashi
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan

Daisuke Doi, Tetsuhiro Kikuchi, Asuka Morizane, Satoe Hiramatsu & Jun Takahashi
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

Takayuki Kikuchi, Yoshiki Arakawa & Susumu Miyamoto
Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

Yasutaka Fushimi, Tomohisa Okada & Yuji Nakamoto
Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

Takayuki Anazawa
Department of Hematology/Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Takero Shindo
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Kentaro Ueno & Satoshi Morita

Contributions

J.T. and R.T. were the lead investigators. N.S., D.D. and Takayuki Kikuchi wrote the first draft of the paper. N.S., E.N., M.S., H.Y., Y.T., A.S., Y.F., T.O., Y.N. and R.T. contributed to the acquisition of clinical data. D.D., Tetsuhiro Kikuchi, A.M. and J.T. contributed to the generation of human iPS cells and DA progenitor cells. S.H. contributed to the PD rat experiments. Takayuki Kikuchi, Y.A. and S. Miyamoto contributed to neurosurgery. T.A. and T.S. contributed to immunosuppressive therapy management. K.U. and S. Morita performed statistical analyses. All of the authors contributed to the analysis or interpretation of data and performed critical revisions of the manuscript.

Corresponding authors

Correspondence to Ryosuke Takahashi or Jun Takahashi.

Ethics declarations

Competing interests

N.S., R.T. and J.T. received a grant for collaborative research from Sumitomo Pharma. R.T. received a research grant from Nihon Medi-Physics. T.O. received a research grant from Siemens Healthcare. S.H. is an employee of Sumitomo Pharma. The other authors declare no competing interests.

Peer review

Peer review information

Nature thanks David Devos, Hideyuki Okano and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.