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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Published inFrontiers in cellular neuroscience Vol. 14; p. 631802
Main Authors Perrier, Stefanie, Michell-Robinson, Mackenzie A, Bernard, Geneviève
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 28.01.2021
Frontiers Media S.A
Subjects
4H leukodystrophy
Age
Ataxia
cell therapy
Cellular Neuroscience
Central nervous system
Disease
gene editing
Gene expression
Gene therapy
Genotype & phenotype
Hypogonadism
hypomyelination
Intellectual disabilities
Leukodystrophy
Magnetic resonance imaging
Myelin
Neurodegeneration
POLR3-related leukodystrophy
Proteins
RNA polymerase
Substantia alba
Transplantation
POLR3-related leukodystrophy
gene therapy
4H leukodystrophy
hypomyelination
gene editing
cell therapy
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Summary: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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Specialty section: This article was submitted to Cellular Neuropathology, a section of the journal Frontiers in Cellular Neuroscience
Edited by: Dominik Fröhlich, University of New South Wales, Australia
Reviewed by: Bilal Ersen Kerman, Istanbul Medipol University, Turkey; Robert Weissert, University of Regensburg, Germany
These authors have contributed equally to this work
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2020.631802