@article{97e0d4603e164b39b285bdbaaacf8d3b,
title = "Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD",
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.",
keywords = "ATMP, Parkinson's, clinical trial, dopamine, minipig, neurosurgery, neurosurgical, pluripotent, regulatory, stem cell therapy, transplantation, Human Embryonic Stem Cells, Humans, Rats, Parkinson Disease/therapy, Tissue Distribution, Animals, Stem Cell Transplantation/methods, Cell Differentiation/physiology, Dopaminergic Neurons/physiology",
author = "Agnete Kirkeby and Jenny Nelander and Hoban, {Deirdre B} and Nina Rogelius and Hj{\'a}lmar Bjartmarz and {Novo Nordisk Cell Therapy R&D} and Petter Storm and Alessandro Fiorenzano and Adler, {Andrew F} and Shelby Vale and Janitha Mudannayake and Yu Zhang and Tiago Cardoso and Bengt Mattsson and Landau, {Anne M} and Glud, {Andreas N} and S{\o}rensen, {Jens C} and Lillethorup, {Thea P} and Mark Lowdell and Carla Carvalho and Owen Bain and {van Vliet}, Trinette and Olle Lindvall and Anders Bj{\"o}rklund and Bronwen Harry and Emma Cutting and H{\aa}kan Widner and Gesine Paul and Barker, {Roger A} and Malin Parmar",
year = "2023",
month = oct,
doi = "10.1016/j.stem.2023.08.014",
language = "English",
volume = "30",
pages = "1299--1314.e9",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "10",
}