Sawamoto Nobukatsu, Doi Daisuke, Nakanishi Etsuro, Sawamura Masanori, Kikuchi Takayuki, Yamakado Hodaka, Taruno Yosuke, Shima Atsushi, Fushimi Yasutaka, Okada Tomohisa, Kikuchi Tetsuhiro, Morizane Asuka, Hiramatsu Satoe, Anazawa Takayuki, Shindo Takero, Ueno Kentaro, Morita Satoshi, Arakawa Yoshiki, Nakamoto Yuji, Miyamoto Susumu, Takahashi Ryosuke, Takahashi Jun
Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Nature. 2025 May;641(8064):971-977. doi: 10.1038/s41586-025-08700-0. Epub 2025 Apr 16.
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 concerns. Pluripotent stem (PS) cells emerged as a promising alternative for developing safe and effective treatments. 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 (F-DOPA) influx rate constant (K) 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.
帕金森病是由多巴胺神经元丧失引起的,会导致运动症状。最初使用胎儿组织的细胞疗法显示出前景,但存在并发症和伦理问题。多能干细胞(PS细胞)成为开发安全有效治疗方法的有希望的替代方案。在京都大学医院进行的这项I/II期试验中,7名患者(年龄在50 - 69岁之间)接受了源自诱导多能干细胞(iPS细胞)的多巴胺能祖细胞的双侧移植。主要结局关注安全性和不良事件,而次要结局评估24个月内的运动症状变化和多巴胺生成情况。没有严重不良事件,有73起轻度至中度事件。除非需要进行治疗调整,否则患者的抗帕金森病药物剂量维持不变,这导致异动症增加。磁共振成像显示没有移植物过度生长。在接受疗效评估的6名患者中,4名患者的运动障碍协会统一帕金森病评定量表第三部分“关”期评分有所改善,5名患者的“开”期评分有所改善。所有6名患者的“关”期和“开”期评分的平均变化分别为9.5分(20.4%)和4.3分(35.7%)。4名患者的Hoehn - Yahr分期有所改善。壳核中氟 - 18 - L - 二羟基苯丙氨酸(F - DOPA)流入速率常数(K)值增加了44.7%,高剂量组的增加幅度更大。其他指标变化极小。这项试验(jRCT2090220384)表明,异体iPS细胞衍生的多巴胺能祖细胞能够存活、产生多巴胺且不会形成肿瘤,因此提示对帕金森病具有安全性和潜在临床益处。