Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease

• 成果类型: Article
• 署名作者: 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.
• 署名单位: Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; University of Toronto; Krembil Research Institute; University of Toronto; University of Toronto; University Health Network Toronto; Northwell Health; Northwell Health; Memorial Sloan Kettering Cancer Center; University of California System; University of California Irvine
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2925
• DOI: 10.1038/s41586-025-08845-y
• 发表日期: 2025-05-22
• 关键词: long-term survival; intrastriatal transplantation; DOUBLE-BLIND; grafts; improvement; efficacy; safety

摘要

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 (0.9 million cells, n = 5) and a high-dose (2.7 million 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 18 months 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.