Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson’s disease by Nobukatsu Sawamoto1,8, Daisuke Doi2,8, Etsuro Nakanishi1,8, Masanori Sawamura1,8, ISBN 101038/S41586025087000 instant download

Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson’s disease by Nobukatsu Sawamoto1,8, Daisuke Doi2,8, Etsuro Nakanishi1,8, Masanori Sawamura1,8, ISBN 101038/S41586025087000 instant download

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 efective 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 efcacy evaluation, four showed improvements in the Movement Disorder Society Unifed Parkinson’s Disease Rating Scale part III OFF score, and fve 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) infux 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 benefts for Parkinson’s disease.