Barker Roger A, Lao-Kaim Nicholas P, Guzman Natalie Valle, Athauda Dilan, Bjartmarz Hjalmar, Björklund Anders, Church Alistair, Cutting Emma, Daft Danielle, Dayal Viswas, Dunnett Stephen, Evans Amy, Grealish Shane, Hannaway Naomi, He Xiaoling, Hewitt Sam, Kefalopoulou Zinovia, Mahlknecht Philipp, Martín-Bastida Antonio, Farrell Krista, Moore Sarah, Bulstrode Harry, Nakornchai Tagore, Nelander-Wahlestedt Jenny, Roupé Linnea, Paul Gesine, Peall Kathryn, Rosser Anne, Roca-Fernández Adriana, Rowlands Sophie, McGorrian Anne-Marie, Scherf Caroline, Vinh Ngoc Nga, Roberton Victoria, Kelly Claire, Lelos Mariah, Torres Eduardo, Shires Kate, Hills Rachel, Williams Debbie, Roussakis Andreas-Antonios, Sibley Krista, Tyers Pamela, Wijeyekoon Ruwani, Williams-Gray Caroline, Foltynie Thomas, Piccini Paola, Morris Robert, Lazic Stanley E, Lindvall Olle, Parmar Malin, Widner Hakan
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences and Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, UK.
Nat Biotechnol. 2025 May 2. doi: 10.1038/s41587-025-02567-2.
Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson's disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial ( NCT01898390 ) was designed to determine whether this approach could be further developed into a clinically useful treatment. Owing to poor availability of human fetal ventral mesencephalic tissue, only 11 individuals were grafted at two centers using the same tissue preparation protocol but different implantation devices. No overall clinical effect was seen for the primary endpoint 3 years after grafting. No major graft-induced dyskinesias were seen, but we observed differences in outcome related to transplant device and/or site. Mean dopamine uptake improved at 18 months in seven individuals according to [F]fluorodopa positron emission tomography imaging but was restored to near-normal levels in only one individual. Our findings highlight the need for a stem cell source of dopamine neurons for potential Parkinson's disease cell therapy and provide critical insights into how such clinical studies should be approached.
将人胎儿腹侧中脑组织移植到帕金森病患者体内已产生临床益处，但也有副作用，如移植诱导的运动障碍。开放标签的泛欧试验（NCT01898390）旨在确定这种方法是否可以进一步发展成为一种临床上有用的治疗方法。由于人胎儿腹侧中脑组织的可获得性差，只有11名个体在两个中心接受移植，使用相同的组织制备方案但不同的植入装置。移植后3年，主要终点未观察到总体临床效果。未观察到严重的移植诱导的运动障碍，但我们观察到与移植装置和/或部位相关的结果差异。根据[F]氟多巴正电子发射断层扫描成像，7名个体在18个月时平均多巴胺摄取有所改善，但只有1名个体恢复到接近正常水平。我们的研究结果强调了需要一种用于潜在帕金森病细胞治疗的多巴胺神经元干细胞来源，并为如何进行此类临床研究提供了关键见解。
