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

Nobukatsu Sawamoto, Daisuke Doi, Etsuro Nakanishi, Masanori Sawamura, Takayuki Kikuchi, Hodaka Yamakado, Yosuke Taruno, Atsushi Shima, Yasutaka Fushimi, Tomohisa Okada, Tetsuhiro Kikuchi, Asuka Morizane, Satoe Hiramatsu, Takayuki Anazawa, Takero Shindo, Kentaro Ueno, Satoshi Morita, Yoshiki Arakawa, Yuji Nakamoto, Susumu Miyamoto, Ryosuke Takahashi () and Jun Takahashi ()
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Nobukatsu Sawamoto: Kyoto University Graduate School of Medicine
Daisuke Doi: Kyoto University
Etsuro Nakanishi: Kyoto University Graduate School of Medicine
Masanori Sawamura: Kyoto University Graduate School of Medicine
Takayuki Kikuchi: Kyoto University Graduate School of Medicine
Hodaka Yamakado: Kyoto University Graduate School of Medicine
Yosuke Taruno: Kyoto University Graduate School of Medicine
Atsushi Shima: Kyoto University Graduate School of Medicine
Yasutaka Fushimi: Kyoto University Graduate School of Medicine
Tomohisa Okada: Kyoto University Graduate School of Medicine
Tetsuhiro Kikuchi: Kyoto University
Asuka Morizane: Kyoto University
Satoe Hiramatsu: Kyoto University
Takayuki Anazawa: Kyoto University Graduate School of Medicine
Takero Shindo: Kyoto University Graduate School of Medicine
Kentaro Ueno: Kyoto University Graduate School of Medicine
Satoshi Morita: Kyoto University Graduate School of Medicine
Yoshiki Arakawa: Kyoto University Graduate School of Medicine
Yuji Nakamoto: Kyoto University Graduate School of Medicine
Susumu Miyamoto: Kyoto University Graduate School of Medicine
Ryosuke Takahashi: Kyoto University Graduate School of Medicine
Jun Takahashi: Kyoto University

Nature, 2025, vol. 641, issue 8064, 971-977

Abstract: 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 concerns1–5. 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.

Date: 2025
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DOI: 10.1038/s41586-025-08700-0

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