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

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

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Sidor (från-till)	1299-1314
Antal sidor	26
Tidskrift	Cell Stem Cell
Volym	30
Nummer	10
DOI	https://doi.org/10.1016/j.stem.2023.08.014
Status	Published - 2023 okt. 5

Ämnesklassifikation (UKÄ)

Neurologi

FN:s Globala mål

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10.1016/j.stem.2023.08.014Licens: CC BY

STEM-PD-studien
Parmar, M. (PI), Kirkeby, A. (Forskare), Barker, R. (Forskare), Paul-Visse, G. (Forskare), Widner, H. (Forskare), Bjartmarz, H. (Forskare), Nelander, J. (Forskare), Van Vliet, T. (Forskare) & Piccini, P. (Forskare)
The Swedish Parkinson Foundation, Parkinsonfonden, Swedish Research Council
2022/11/01 → …
Projekt: Forskning

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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., ... Novo Nordisk Cell Therapy R&D (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. https://doi.org/10.1016/j.stem.2023.08.014

@article{c071c5b6e71844d9b75e68e25cdd16f7,

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

author = "Agnete Kirkeby and Jenny Nelander and Hoban, {Deirdre B.} and Nina Rogelius and Hj{\'a}lmar Bjartmarz 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 and {Novo Nordisk Cell Therapy R&D}",

year = "2023",

month = oct,

day = "5",

doi = "10.1016/j.stem.2023.08.014",

language = "English",

volume = "30",

pages = "1299--1314",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "10",

}

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 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, nr. 10, s. 1299-1314. https://doi.org/10.1016/j.stem.2023.08.014

TY - JOUR

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 - 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

PY - 2023/10/5

Y1 - 2023/10/5

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 - clinical trial

KW - dopamine

KW - minipig

KW - neurosurgery

KW - neurosurgical

KW - Parkinson's

KW - pluripotent

KW - regulatory

KW - stem cell therapy

KW - transplantation

U2 - 10.1016/j.stem.2023.08.014

DO - 10.1016/j.stem.2023.08.014

M3 - Article

C2 - 37802036

AN - SCOPUS:85174454209

SN - 1934-5909

VL - 30

SP - 1299

EP - 1314

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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FN:s Globala mål

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