Updates on Facioscapulohumeral Muscular Dystrophy (FSHD)

• Published in: Current treatment options in neurology Vol. 26; no. 6; pp. 261 - 275
• Main Authors: Chin, Amanda X. Y., Quak, Zhi Xuan, Chan, Yee Cheun, Quek, Amy M. L., Ng, Kay W. P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 02-04-2024
• Subjects: Critical Care Medicine; Diabetes; Family Medicine; General Practice; Intensive; Internal Medicine; Medicine; Medicine & Public Health; Neurology; Ophthalmology; Review; Topical Collection on Neuromuscular Disorders; Facioscapulohumeral dystrophy; CRISPR gene therapy; Losmapimod; Antisense oligonucleotide; Targeted therapy; DUX4 protein
• ISSN: 1092-8480; 1534-3138
• DOI: 10.1007/s11940-024-00790-x

Purpose of review
This review aims to provide a summary of the pathophysiology, clinical presentation and management options for facioscapulohumeral dystrophy (FSHD). We discuss current management options and delve into updates about developments in targeted therapy.
Recent findings
New breakthroughs in FSHD research have led to a further understanding of aberrant DUX4 protein expression in the underlying pathophysiology of FSHD. This has paved the way for the development of targeted therapies aimed at targeting DUX4 expression or its downstream effects. Therapeutic strategies for FSHD primarily target DUX4 through three main avenues: small molecules, antisense oligonucleotide therapeutics and CRISPR-based approaches. This review discusses these strategies further. Presently, all prospective targeted therapies are in the pre-clinical phase, except for losmapimod, which is currently undergoing a phase 3 clinical trial.
Summary
Given the absence of approved disease-modifying treatments for FSHD, the primary approach for management currently involves multidisciplinary supportive measures which are limited. Recent developments in the form of targeted therapies and strategies for the definitive treatment of FSHD indicate a promising era.