日本京都大学医学院Jun Takahashi小组在研究中取得进展。他们研究出iPS细胞衍生的多巴胺能细胞治疗帕金森病的I/II期试验。该项研究成果发表在2025年4月16日出版的《自然》上。

帕金森氏症的主要症状是多巴胺神经元的丧失，导致运动症状。以胎儿组织为主题的初始细胞治疗显示出希望，但存在并发症和伦理问题。多能干细胞（PS）成为开发安全有效的治疗方法的一个很有前途的选择。在京都大学医院进行的I/II期试验中，7名患者（年龄50-69岁）接受了双侧诱导PS （iPS）细胞衍生的多巴胺能祖细胞移植。主要结局关注安全性和不良事件，次要结局评估24个月的运动症状变化和多巴胺产生。无严重不良事件，轻度至中度事件73例。患者的抗帕金森药物剂量保持不变，除非需要进行治疗调整，导致运动障碍增加。磁共振成像未见移植物过度生长。在6例接受疗效评估的患者中，有4例在运动障碍学会统一帕金森病评定量表第三部分OFF评分中有所改善，5例在ON评分中有所改善。6例患者OFF和ON评分的平均变化分别为9.5分（20.4%）和4.3分（35.7%）。这些患者的Hoehn-Yahr分期得到改善。氟-18- l -二羟基苯丙氨酸（18F-DOPA）壳核内流速率常数（Ki）值升高44.7%，高剂量组升高幅度较大。其他指标显示变化很小。该试验（jRCT2090220384）表明异体iPSs细胞衍生的多巴胺能祖细胞存活，产生多巴胺，不形成肿瘤，因此提示帕金森病的安全性和潜在的临床益处。

附：英文原文

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

Author: 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

Issue&Volume: 2025-04-16

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 24months. 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.

DOI: 10.1038/s41586-025-08700-0

Source: https://www.nature.com/articles/s41586-025-08700-0