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; Novo Nordisk Cell Therapy R&D; 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

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, Novo Nordisk Cell Therapy R&D, 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 CarvalhoOwen Bain, Trinette van Vliet, Olle Lindvall, Anders Björklund, Bronwen Harry, Emma Cutting, Håkan Widner, Gesine Paul, Roger A Barker, Malin Parmar

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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	10
Pages (from-to)	1299-1314.e9
Number of pages	16
ISSN	1934-5909
DOIs	https://doi.org/10.1016/j.stem.2023.08.014
Publication status	Published - Oct 2023

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

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1-s2.0-S1934590923003211-mainFinal published version, 7.13 MBLicence: CC BY

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Kirkeby, A., Nelander, J., Hoban, D. B., Rogelius, N., Bjartmarz, H., Novo Nordisk Cell Therapy R&D, 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., ... Parmar, M. (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

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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.",

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",

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pages = "1299--1314.e9",

journal = "Cell Stem Cell",

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Kirkeby, A, Nelander, J, Hoban, DB, Rogelius, N, Bjartmarz, H, Novo Nordisk Cell Therapy R&D, 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 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

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 et al.
In: Cell Stem Cell, Vol. 30, No. 10, 10.2023, p. 1299-1314.e9.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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T1 - Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD

AU - Kirkeby, Agnete

AU - Nelander, Jenny

AU - Hoban, Deirdre B

AU - Rogelius, Nina

AU - Bjartmarz, Hjálmar

AU - Novo Nordisk Cell Therapy R&D

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

PY - 2023/10

Y1 - 2023/10

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.

KW - ATMP

KW - Parkinson's

KW - clinical trial

KW - dopamine

KW - minipig

KW - neurosurgery

KW - neurosurgical

KW - pluripotent

KW - regulatory

KW - stem cell therapy

KW - transplantation

KW - Human Embryonic Stem Cells

KW - Humans

KW - Rats

KW - Parkinson Disease/therapy

KW - Tissue Distribution

KW - Animals

KW - Stem Cell Transplantation/methods

KW - Cell Differentiation/physiology

KW - Dopaminergic Neurons/physiology

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U2 - 10.1016/j.stem.2023.08.014

DO - 10.1016/j.stem.2023.08.014

M3 - Journal article

C2 - 37802036

SN - 1934-5909

VL - 30

SP - 1299-1314.e9

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 10

ER -

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

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