The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease
Roger A. Barker, Nicholas P Lao–Kaim, Natalie Valle Guzman, Dilan Athauda, Hjálmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen B. Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín‐Bastida, Krista Farrell, Sarah A. Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn J. Peall, Anne Rosser, Adriana Roca‐Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria H. Roberton, Claire Kelly, Mariah J. Lelos, Eduardo M. Torres, K.L. Shires, Rachel Hills, Debbie Williams, Andreas–Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert C. Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Håkan Widner, Hakan Widner, Hjalmar Bjartmarz, Anders Björklund, Olle Lindvall, Jenny Nelander-Wahlestedt, Linnea Roupé, Malin Parmar, Gesine Paul
Abstract
Abstract 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 [ 18 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.