TY - JOUR

T1 - Translating cell therapies for neurodegenerative diseases

T2 - Huntington's disease as a model disorder

AU - Rosser, Anne E.

AU - Busse, Monica E.

AU - Gray, William P.

AU - Badin, Romina Aron

AU - Perrier, Anselme L.

AU - Wheelock, Vicki

AU - Cozzi, Emanuele

AU - Martin, Unai Perpina

AU - Salado-Manzano, Cristina

AU - Mills, Laura J.

AU - Drew, Cheney

AU - Goldman, Steven A.

AU - Canals, Josep M.

AU - Thompson, Leslie M.

AU - SC4HD Members

PY - 2022

Y1 - 2022

N2 - 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.Rosser et al. discuss the challenges associated with clinical translation of cell therapies, using Huntington's disease as the primary example. They suggest strategies to address these challenges, based on the consensus view emerging from international workshops and discussion within the platform 'Stem Cells for Huntington's Disease'.

AB - 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.Rosser et al. discuss the challenges associated with clinical translation of cell therapies, using Huntington's disease as the primary example. They suggest strategies to address these challenges, based on the consensus view emerging from international workshops and discussion within the platform 'Stem Cells for Huntington's Disease'.

KW - cell therapy

KW - stem cells

KW - clinical translation

KW - neurodegeneration

KW - Huntington's

KW - FETAL STRIATAL TRANSPLANTATION

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - STEM-CELLS

KW - DOPAMINERGIC-NEURONS

KW - NEURAL TRANSPLANTATION

KW - FUNCTIONAL RECOVERY

KW - PARKINSONS-DISEASE

KW - RANDOMIZED-TRIALS

KW - IMMUNE REJECTION

KW - CLINICAL-TRIALS

U2 - 10.1093/brain/awac086

DO - 10.1093/brain/awac086

M3 - Review

C2 - 35262656

VL - 145

SP - 1584

EP - 1597

JO - Brain

JF - Brain

SN - 0006-8950

IS - 5

ER -