美国加州大学C. Henchcliffe课题组的最新研究提出了hES细胞来源的多巴胺能神经元治疗帕金森病的I期试验。相关论文于2025年4月16日发表于国际顶尖学术期刊《自然》杂志上。

课题组人员报告了一项开放标签I期临床试验（NCT04802733）的结果，该试验将一种冷冻保存的、现成的多巴胺能神经元祖细胞产品（bemdaneprocel）从人类胚胎干细胞（hES）中提取，并移植到帕金森病患者的双侧壳核中。12例患者按顺序分为两组：低剂量组(90万细胞，n=5)和高剂量(270万细胞，n= 7)队列，所有参与者接受一年的免疫抑制。该试验达到了移植后一年的安全性和耐受性的主要目标，没有与细胞产物相关的不良事件。移植后18个月，皮膜18 -氟多巴正电子发射断层扫描摄取增加，表明移植物存活。次要和探索性临床结果显示改善或稳定，包括运动障碍学会统一帕金森病评定量表（MDS-UPDRS）第三部分OFF评分在高剂量队列中平均提高23分。没有移植物引起的运动障碍。这些数据证明了安全性，并支持未来明确的临床研究。

据介绍，帕金森氏症是一种进行性神经退行性疾病，具有相当大的健康和经济负担。它的特征是中脑多巴胺能神经元的丧失，随着疾病的进展，对症药物或手术治疗的反应减弱。细胞治疗的目的是通过纹状体内移植来补充丢失的多巴胺能神经元及其纹状体突起。

附：英文原文

Title: Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease

Author: Tabar, V., Sarva, H., Lozano, A. M., Fasano, A., Kalia, S. K., Yu, K. K. H., Brennan, C., Ma, Y., Peng, S., Eidelberg, D., Tomishima, M., Irion, S., Stemple, W., Abid, N., Lampron, A., Studer, L., Henchcliffe, C.

Issue&Volume: 2025-04-16

Abstract: Parkinson’s disease is a progressive neurodegenerative condition with a considerable health and economic burden1. It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses2. Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational cryopreserved, off-the-shelf dopaminergic neuron progenitor cell product (bemdaneprocel) derived from human embryonic stem (hES) cells and grafted bilaterally into the putamen of patients with Parkinson’s disease. Twelve patients were enrolled sequentially in two cohorts—a low-dose (0.9million cells, n=5) and a high-dose (2.7million cells, n=7) cohort—and all of the participants received one year of immunosuppression. The trial achieved its primary objectives of safety and tolerability one year after transplantation, with no adverse events related to the cell product. At 18months after grafting, putaminal 18Fluoro-DOPA positron emission tomography uptake increased, indicating graft survival. Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort. There were no graft-induced dyskinesias. These data demonstrate safety and support future definitive clinical studies.

DOI: 10.1038/s41586-025-08845-y

Source: https://www.nature.com/articles/s41586-025-08845-y