학술논문
Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD
Document Type
Author
Kirkeby, Agnete; Nelander, Jenny; Hoban, Deirdre B.; Rogelius, Nina; Bjartmarz, Hjálmar; Storm, Petter; Fiorenzano, Alessandro; Adler, Andrew F.; Vale, Shelby; Mudannayake, Janitha; Zhang, Yu; Cardoso, Tiago; Mattsson, Bengt; Landau, Anne M.; Glud, Andreas N.; Sørensen, Jens C.; Lillethorup, Thea P.; Lowdell, Mark; Carvalho, Carla; Bain, Owen; van Vliet, Trinette; Lindvall, Olle; Björklund, Anders; Harry, Bronwen; Cutting, Emma; Widner, Håkan; Paul, Gesine; Barker, Roger A.; Parmar, Malin
Source
Cell Stem Cell StemTherapy: National Initiative on Stem Cells for Regenerative Therapy MultiPark: Multidisciplinary research focused on Parkinson´s disease. 30(10):1299-1314
Subject
Language
English
ISSN
1934-5909
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.