Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD.

Autor:	Kirkeby A; Wallenberg Neuroscience Center, Wallenberg Center for Molecular Medicine and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW) and Department of Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: agnete.kirkeby@med.lu.se., Nelander J; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Hoban DB; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Rogelius N; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Bjartmarz H; Department of Neurosurgery, Skåne University Hospital, 221 85 Lund, Sweden., Storm P; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Fiorenzano A; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Adler AF; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Vale S; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Mudannayake J; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Zhang Y; Wallenberg Neuroscience Center, Wallenberg Center for Molecular Medicine and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Cardoso T; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Mattsson B; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Landau AM; Department of Nuclear Medicine & PET-Center and Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Glud AN; Center for Experimental Neuroscience (CENSE), Department of Neurosurgery, Department of Clinical Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark., Sørensen JC; Center for Experimental Neuroscience (CENSE), Department of Neurosurgery, Department of Clinical Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark., Lillethorup TP; Department of Nuclear Medicine & PET-Center and Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark., Lowdell M; Centre for Cell, Gene and Tissue Therapeutics, Royal Free NHS Foundation Trust, Royal Free Hospital, London NW3 2QG, UK., Carvalho C; Centre for Cell, Gene and Tissue Therapeutics, Royal Free NHS Foundation Trust, Royal Free Hospital, London NW3 2QG, UK., Bain O; Centre for Cell, Gene and Tissue Therapeutics, Royal Free NHS Foundation Trust, Royal Free Hospital, London NW3 2QG, UK., van Vliet T; Department of Neurology, Skåne University Hospital, 221 85 Lund, Sweden., Lindvall O; Lund Stem Cell Center and Department of Clinical Sciences Lund, Lund University, 221 84 Lund, Sweden., Björklund A; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden., Harry B; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK., Cutting E; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK., Widner H; Department of Neurology, Skåne University Hospital, 221 85 Lund, Sweden., Paul G; Department of Neurology, Skåne University Hospital, 221 85 Lund, Sweden; Wallenberg Neuroscience Center, Wallenberg Center for Molecular Medicine, Department of Clinical Sciences, Lund University, 221 84 Lund, Sweden., Barker RA; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge CB2 0AW, UK., Parmar M; Wallenberg Neuroscience Center, MultiPark and Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden. Electronic address: malin.parmar@med.lu.se.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2023 Oct 05; Vol. 30 (10), pp. 1299-1314.e9.
DOI:	10.1016/j.stem.2023.08.014
Abstrakt:	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. Competing Interests: Declaration of interests M.P. is the owner of Parmar Cells AB. A.K. is the owner of Kirkeby Cell Therapy APS. M.P. and A.K. are co-inventors on patents WO2016162747A2/A3 and WO2019016113A1. M.P., A.K., R.A.B., H.W., H.B., A.B., E.C., D.B.H., G.P., and B.H. have performed paid consultancy for Novo Nordisk A/S, and members of NNCT R&D are current or previous employees of Novo Nordisk A/S. T.C., A.F.A., Y.Z., S.V., and D.B.H. performed the work as employees of Lund University but are currently employed by Novo Nordisk A/S (T.C., A.F.A., and S.V.), Takara Bio (Y.Z.), and D.B.H. at Eli Lilly and Company, where she is also a minor share holder. Novo Nordisk A/S is developing the STEM-PD product for commercial use. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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