韩国延世大学Dong-Wook Kim团队的研究开发出了hESC来源的多巴胺祖细胞治疗帕金森病的1/2a期临床试验。相关论文于2025年10月13日发表在《细胞》杂志上。
该课题组从人胚胎干细胞中获得了高纯度的多巴胺能祖细胞（A9-DPCs），并在一项针对PD患者的单中心、开放标签、剂量递增的1/2a期试验（NCT05887466）中评估了它们的安全性和实验性有效性。12例中重度PD患者接受低剂量（315万个细胞，n = 6）或高剂量（630万个细胞，n = 6）免疫抑制的A9-DPC双侧壳核移植。未观察到剂量限制性毒性或移植物相关不良事件。12个月时，停药期运动障碍学会统一帕金森病评定量表（MDS-UPDRS）第三部分评分和Hoehn和Yahr分期均有所改善，高剂量组运动改善更大。多巴胺转运体正电子发射断层扫描（PET）成像显示，移植后高剂量组后壳核摄取增加，摄取更大，支持移植物存活。这些结果表明，双侧A9-DPC移植是安全的，并可能改善PD患者的帕金森运动症状。
据了解，长期以来，帕金森病（PD）一直被认为是细胞替代疗法的合适候选者。
附：英文原文
Title: Phase 1/2a clinical trial of hESC-derived dopamine progenitors in Parkinson’s disease
Author: Jin Woo Chang, Han Kyu Na, Kyung Won Chang, Chan Wook Park, Do-Hun Kim, Sanghyun Park, Chul-Yong Park, Jang Hyeon Eom, Seung Taek Nam, Ki-Sang Jo, Mi-Young Jo, Sung Kyoung Choi, Hye-Jin Hur, Sarang Kim, Minseok Kim, Dae-Sung Kim, Dong-Youn Hwang, Myoung Soo Kim, Inkyung Jung, Jongwan Kim, Myung Soo Cho, Phil Hyu Lee, Dong-Wook Kim
Issue&Volume: 2025-10-13
Abstract: Parkinson’s disease (PD) has long been considered an appropriate candidate for cell replacement therapy. We generated high-purity dopaminergic progenitors (A9-DPCs) from human embryonic stem cells and evaluated their safety and exploratory efficacy in a single-center, open-label, dose-escalation phase 1/2a trial (NCT05887466) for PD patients. Twelve patients with moderate-to-severe PD received bilateral putamen transplantation of low-dose (3.15 million cells; n = 6) or high-dose (6.30 million cells; n = 6) A9-DPC with immunosuppression. No dose-limiting toxicities or graft-related adverse events were observed. At 12 months, off-medication Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III scores and Hoehn and Yahr stage improved, with greater motor improvements in the high-dose group. Dopamine transporter positron emission tomography (PET) imaging showed increased posterior putamen uptake with greater uptake in the high-dose group after transplantation, supporting graft survival. These findings indicate that bilateral transplantation of A9-DPC is safe and may improve parkinsonian motor symptoms in patients with PD.
DOI: 10.1016/j.cell.2025.09.010
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01041-4