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POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches

Leukodystrophies are a class of rare inherited central nervous system (CNS) disorders that affect the white matter of the brain, typically leading to progressive neurodegeneration and early death. Hypomyelinating leukodystrophies are characterized by the abnormal formation of the myelin sheath durin...

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Autores principales: Perrier, Stefanie, Michell-Robinson, Mackenzie A., Bernard, Geneviève
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902007/
https://www.ncbi.nlm.nih.gov/pubmed/33633543
http://dx.doi.org/10.3389/fncel.2020.631802
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author Perrier, Stefanie
Michell-Robinson, Mackenzie A.
Bernard, Geneviève
author_facet Perrier, Stefanie
Michell-Robinson, Mackenzie A.
Bernard, Geneviève
author_sort Perrier, Stefanie
collection PubMed
description Leukodystrophies are a class of rare inherited central nervous system (CNS) disorders that affect the white matter of the brain, typically leading to progressive neurodegeneration and early death. Hypomyelinating leukodystrophies are characterized by the abnormal formation of the myelin sheath during development. POLR3-related or 4H (hypomyelination, hypodontia, and hypogonadotropic hypogonadism) leukodystrophy is one of the most common types of hypomyelinating leukodystrophy for which no curative treatment or disease-modifying therapy is available. This review aims to describe potential therapies that could be further studied for effectiveness in pre-clinical studies, for an eventual translation to the clinic to treat the neurological manifestations associated with POLR3-related leukodystrophy. Here, we discuss the therapeutic approaches that have shown promise in other leukodystrophies, as well as other genetic diseases, and consider their use in treating POLR3-related leukodystrophy. More specifically, we explore the approaches of using stem cell transplantation, gene replacement therapy, and gene editing as potential treatment options, and discuss their possible benefits and limitations as future therapeutic directions.
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spelling pubmed-79020072021-02-24 POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches Perrier, Stefanie Michell-Robinson, Mackenzie A. Bernard, Geneviève Front Cell Neurosci Cellular Neuroscience Leukodystrophies are a class of rare inherited central nervous system (CNS) disorders that affect the white matter of the brain, typically leading to progressive neurodegeneration and early death. Hypomyelinating leukodystrophies are characterized by the abnormal formation of the myelin sheath during development. POLR3-related or 4H (hypomyelination, hypodontia, and hypogonadotropic hypogonadism) leukodystrophy is one of the most common types of hypomyelinating leukodystrophy for which no curative treatment or disease-modifying therapy is available. This review aims to describe potential therapies that could be further studied for effectiveness in pre-clinical studies, for an eventual translation to the clinic to treat the neurological manifestations associated with POLR3-related leukodystrophy. Here, we discuss the therapeutic approaches that have shown promise in other leukodystrophies, as well as other genetic diseases, and consider their use in treating POLR3-related leukodystrophy. More specifically, we explore the approaches of using stem cell transplantation, gene replacement therapy, and gene editing as potential treatment options, and discuss their possible benefits and limitations as future therapeutic directions. Frontiers Media S.A. 2021-01-28 /pmc/articles/PMC7902007/ /pubmed/33633543 http://dx.doi.org/10.3389/fncel.2020.631802 Text en Copyright © 2021 Perrier, Michell-Robinson and Bernard. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Perrier, Stefanie
Michell-Robinson, Mackenzie A.
Bernard, Geneviève
POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches
title POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches
title_full POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches
title_fullStr POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches
title_full_unstemmed POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches
title_short POLR3-Related Leukodystrophy: Exploring Potential Therapeutic Approaches
title_sort polr3-related leukodystrophy: exploring potential therapeutic approaches
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902007/
https://www.ncbi.nlm.nih.gov/pubmed/33633543
http://dx.doi.org/10.3389/fncel.2020.631802
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