Agnete Kirkeby, Jenny Nelander, Deirdre B Hoban, Nina Rogelius, Hjálmar Bjartmarz, Petter Storm, Alessandro Fiorenzano, Andrew F Adler, Shelby Vale, Janitha Mudannayake, Yu Zhang, Tiago Cardoso, Bengt Mattsson, Anne M Landau, Andreas N Glud, Jens C Sørensen, Thea P Lillethorup, Mark Lowdell, Carla Carvalho, Owen Bain, Trinette van Vliet, Olle Lindvall, Anders Björklund, Bronwen Harry, Emma Cutting, Håkan Widner, Gesine Paul, Roger A Barker, Malin Parmar
{"title":"Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD.","authors":"Agnete Kirkeby, Jenny Nelander, Deirdre B Hoban, Nina Rogelius, Hjálmar Bjartmarz, Petter Storm, Alessandro Fiorenzano, Andrew F Adler, Shelby Vale, Janitha Mudannayake, Yu Zhang, Tiago Cardoso, Bengt Mattsson, Anne M Landau, Andreas N Glud, Jens C Sørensen, Thea P Lillethorup, Mark Lowdell, Carla Carvalho, Owen Bain, Trinette van Vliet, Olle Lindvall, Anders Björklund, Bronwen Harry, Emma Cutting, Håkan Widner, Gesine Paul, Roger A Barker, Malin Parmar","doi":"10.1016/j.stem.2023.08.014","DOIUrl":null,"url":null,"abstract":"<p><p>Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.stem.2023.08.014","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.
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