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Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder

There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across...

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Autores principales: Rosser, Anne E., Busse, Monica E., Gray, William P., Badin, Romina Aron, Perrier, Anselme L., Wheelock, Vicki, Cozzi, Emanuele, Martin, Unai Perpiña, Salado-Manzano, Cristina, Mills, Laura J., Drew, Cheney, Goldman, Steven A., Canals, Josep M., Thompson, Leslie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166564/
https://www.ncbi.nlm.nih.gov/pubmed/35262656
http://dx.doi.org/10.1093/brain/awac086
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author Rosser, Anne E.
Busse, Monica E.
Gray, William P.
Badin, Romina Aron
Perrier, Anselme L.
Wheelock, Vicki
Cozzi, Emanuele
Martin, Unai Perpiña
Salado-Manzano, Cristina
Mills, Laura J.
Drew, Cheney
Goldman, Steven A.
Canals, Josep M.
Thompson, Leslie M.
author_facet Rosser, Anne E.
Busse, Monica E.
Gray, William P.
Badin, Romina Aron
Perrier, Anselme L.
Wheelock, Vicki
Cozzi, Emanuele
Martin, Unai Perpiña
Salado-Manzano, Cristina
Mills, Laura J.
Drew, Cheney
Goldman, Steven A.
Canals, Josep M.
Thompson, Leslie M.
author_sort Rosser, Anne E.
collection PubMed
description There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington’s disease as a specific example, and suggest potential strategies to address these challenges. Huntington’s disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington’s disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington’s Disease and the European Huntington’s Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington’s disease.
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spelling pubmed-91665642022-06-06 Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder Rosser, Anne E. Busse, Monica E. Gray, William P. Badin, Romina Aron Perrier, Anselme L. Wheelock, Vicki Cozzi, Emanuele Martin, Unai Perpiña Salado-Manzano, Cristina Mills, Laura J. Drew, Cheney Goldman, Steven A. Canals, Josep M. Thompson, Leslie M. Brain Review Article There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment. Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington’s disease as a specific example, and suggest potential strategies to address these challenges. Huntington’s disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington’s disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington’s Disease and the European Huntington’s Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington’s disease. Oxford University Press 2022-03-09 /pmc/articles/PMC9166564/ /pubmed/35262656 http://dx.doi.org/10.1093/brain/awac086 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Rosser, Anne E.
Busse, Monica E.
Gray, William P.
Badin, Romina Aron
Perrier, Anselme L.
Wheelock, Vicki
Cozzi, Emanuele
Martin, Unai Perpiña
Salado-Manzano, Cristina
Mills, Laura J.
Drew, Cheney
Goldman, Steven A.
Canals, Josep M.
Thompson, Leslie M.
Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder
title Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder
title_full Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder
title_fullStr Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder
title_full_unstemmed Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder
title_short Translating cell therapies for neurodegenerative diseases: Huntington’s disease as a model disorder
title_sort translating cell therapies for neurodegenerative diseases: huntington’s disease as a model disorder
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166564/
https://www.ncbi.nlm.nih.gov/pubmed/35262656
http://dx.doi.org/10.1093/brain/awac086
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