Version 1
: Received: 20 July 2024 / Approved: 22 July 2024 / Online: 22 July 2024 (11:53:34 CEST)
How to cite:
Beck, S. L.; Yokota, T. Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape. Preprints2024, 2024071712. https://doi.org/10.20944/preprints202407.1712.v1
Beck, S. L.; Yokota, T. Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape. Preprints 2024, 2024071712. https://doi.org/10.20944/preprints202407.1712.v1
Beck, S. L.; Yokota, T. Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape. Preprints2024, 2024071712. https://doi.org/10.20944/preprints202407.1712.v1
APA Style
Beck, S. L., & Yokota, T. (2024). Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape. Preprints. https://doi.org/10.20944/preprints202407.1712.v1
Chicago/Turabian Style
Beck, S. L. and Toshifumi Yokota. 2024 "Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape" Preprints. https://doi.org/10.20944/preprints202407.1712.v1
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy, characterized by progressive and asymmetric muscle atrophy, primarily affecting muscles of the face, shoulder girdle, and upper arms before affecting muscles of the lower extremities with age and greater disease severity. FSHD is a disabling condition, and patients may also present with various extramuscular symptoms. FSHD is caused by the aberrant expression of double homeobox 4 (DUX4) in adult skeletal muscle, arising from compromised epigenetic repression of the D4Z4 array. DUX4 encodes the DUX4 protein, a transcription factor that activates myotoxic gene programs to produce the FSHD pathology. Therefore, sequence-specific oligonucleotides aimed at reducing DUX4 levels in patients is a compelling therapeutic approach, and one that has received considerable research interest over the last decade. This review aims to describe the current preclinical landscape of oligonucleotide therapies for FSHD. This includes outlining the mechanism of action of each therapy and summarizing the preclinical results obtained regarding their efficacy in cellular and/or murine disease models. The scope of this review is limited to oligonucleotide-based therapies that inhibit the DUX4 gene, mRNA, or protein in a way that does not involve gene editing.
Keywords
facioscapulohumeral muscular dystrophy (FSHD); DUX4; antisense oligonucleotides; RNAi; CRISPR; DNA aptamers; DNA decoys; targeted therapy; genetic therapy
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
