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

Kirkeby, Agnete LU ; Nelander, Jenny LU orcid ; Hoban, Deirdre B. LU ; Rogelius, Nina LU orcid ; Bjartmarz, Hjálmar LU ; Storm, Petter LU orcid ; Fiorenzano, Alessandro LU ; Adler, Andrew F. LU ; Vale, Shelby and Mudannayake, Janitha LU orcid , et al. (2023) In Cell Stem Cell 30(10). p.1299-1314
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... (More)

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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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATMP, clinical trial, dopamine, minipig, neurosurgery, neurosurgical, Parkinson's, pluripotent, regulatory, stem cell therapy, transplantation
in
Cell Stem Cell
volume
30
issue
10
pages
26 pages
publisher
Cell Press
external identifiers
  • pmid:37802036
  • scopus:85174454209
ISSN
1934-5909
DOI
10.1016/j.stem.2023.08.014
language
English
LU publication?
yes
id
c071c5b6-e718-44d9-b75e-68e25cdd16f7
date added to LUP
2023-11-08 10:48:57
date last changed
2024-04-20 02:44:01
@article{c071c5b6-e718-44d9-b75e-68e25cdd16f7,
  abstract     = {{<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>}},
  author       = {{Kirkeby, Agnete and Nelander, Jenny and Hoban, Deirdre B. and Rogelius, Nina and Bjartmarz, Hjálmar and Storm, Petter and Fiorenzano, Alessandro and Adler, Andrew F. and Vale, Shelby and Mudannayake, Janitha and Zhang, Yu and Cardoso, Tiago and Mattsson, Bengt and Landau, Anne M. and Glud, Andreas N. and Sørensen, Jens C. and Lillethorup, Thea P. and Lowdell, Mark and Carvalho, Carla and Bain, Owen and van Vliet, Trinette and Lindvall, Olle and Björklund, Anders and Harry, Bronwen and Cutting, Emma and Widner, Håkan and Paul, Gesine and Barker, Roger A. and Parmar, Malin}},
  issn         = {{1934-5909}},
  keywords     = {{ATMP; clinical trial; dopamine; minipig; neurosurgery; neurosurgical; Parkinson's; pluripotent; regulatory; stem cell therapy; transplantation}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  pages        = {{1299--1314}},
  publisher    = {{Cell Press}},
  series       = {{Cell Stem Cell}},
  title        = {{Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD}},
  url          = {{http://dx.doi.org/10.1016/j.stem.2023.08.014}},
  doi          = {{10.1016/j.stem.2023.08.014}},
  volume       = {{30}},
  year         = {{2023}},
}