Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson’s disease, STEM-PD
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 Nørgaard Glud, Jens Christian Hedemann Sørensen, Thea P. Lillethorup, Mark W. 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
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.