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 N. Glud; Jens C. Sørensen; Thea P. Lillethorup; Mark 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; Novo Nordisk Cell Therapy R&D; Josefine Rågård Christiansen

doi:10.1016/j.stem.2023.08.014

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 N. Glud, Jens C. Sørensen, Thea P. Lillethorup, Mark Lowdell, Carla Carvalho, Owen BainTrinette van Vliet, Olle Lindvall, Anders Björklund, Bronwen Harry, Emma Cutting, Håkan Widner, Gesine Paul, Roger A. Barker, Malin Parmar, Novo Nordisk Cell Therapy R&D, Josefine Rågård Christiansen

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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36 Downloads (Pure)

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.

Original language	English
Journal	Cell Stem Cell
Volume	30
Issue number	10
Pages (from-to)	1299-1314.e9
Number of pages	17
ISSN	1934-5909
DOIs	https://doi.org/10.1016/j.stem.2023.08.014
Publication status	Published - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

ATMP
clinical trial
dopamine
minipig
neurosurgery
neurosurgical
Parkinson's
pluripotent
regulatory
stem cell therapy
transplantation

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Kirkeby, A., Nelander, J., Hoban, D. B., Rogelius, N., Bjartmarz, H., Storm, P., Fiorenzano, A., Adler, A. F., Vale, S., Mudannayake, J., Zhang, Y., Cardoso, T., Mattsson, B., Landau, A. M., Glud, A. N., Sørensen, J. C., Lillethorup, T. P., Lowdell, M., Carvalho, C., ... Christiansen, J. R. (2023). Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD. Cell Stem Cell, 30(10), 1299-1314.e9. https://doi.org/10.1016/j.stem.2023.08.014

Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD. / 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; Novo Nordisk Cell Therapy R&D ; Christiansen, Josefine Rågård (Member of author collaboration).

In: Cell Stem Cell, Vol. 30, No. 10, 2023, p. 1299-1314.e9.

Research output: Contribution to journal › Journal article › Research › peer-review

Kirkeby, A, Nelander, J, Hoban, DB, Rogelius, N, Bjartmarz, H, Storm, P, Fiorenzano, A, Adler, AF, Vale, S, Mudannayake, J, Zhang, Y, Cardoso, T, Mattsson, B, Landau, AM, Glud, AN, Sørensen, JC, Lillethorup, TP, Lowdell, M, Carvalho, C, Bain, O, van Vliet, T, Lindvall, O, Björklund, A, Harry, B, Cutting, E, Widner, H, Paul, G, Barker, RA, Parmar, M, Novo Nordisk Cell Therapy R&D & Christiansen, JR 2023, 'Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD', Cell Stem Cell, vol. 30, no. 10, pp. 1299-1314.e9. https://doi.org/10.1016/j.stem.2023.08.014

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 ; Novo Nordisk Cell Therapy R&D ; Christiansen, Josefine Rågård. / Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD. In: Cell Stem Cell. 2023 ; Vol. 30, No. 10. pp. 1299-1314.e9.

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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.",

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AU - Hoban, Deirdre B.

AU - Rogelius, Nina

AU - Bjartmarz, Hjálmar

AU - Storm, Petter

AU - Fiorenzano, Alessandro

AU - Adler, Andrew F.

AU - Vale, Shelby

AU - Mudannayake, Janitha

AU - Zhang, Yu

AU - Cardoso, Tiago

AU - Mattsson, Bengt

AU - Landau, Anne M.

AU - Glud, Andreas N.

AU - Sørensen, Jens C.

AU - Lillethorup, Thea P.

AU - Lowdell, Mark

AU - Carvalho, Carla

AU - Bain, Owen

AU - van Vliet, Trinette

AU - Lindvall, Olle

AU - Björklund, Anders

AU - Harry, Bronwen

AU - Cutting, Emma

AU - Widner, Håkan

AU - Paul, Gesine

AU - Barker, Roger A.

AU - Parmar, Malin

AU - Novo Nordisk Cell Therapy R&D

A2 - Christiansen, Josefine Rågård

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N2 - 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.

AB - 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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KW - neurosurgical

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KW - regulatory

KW - stem cell therapy

KW - transplantation

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DO - 10.1016/j.stem.2023.08.014

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