Therapeutic Approaches in Facioscapulohumeral Muscular Dystrophy

Trends Mol Med. 2021 Feb;27(2):123-137. doi: 10.1016/j.molmed.2020.09.008. Epub 2020 Oct 19.

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common types of muscular dystrophy, affecting roughly one in 8000 individuals. The complex underlying genetics and poor mechanistic understanding has caused a bottleneck in therapeutic development. Until the discovery of DUX4 and its causal role in FSHD, most trials were untargeted with limited results. Emerging approaches can learn from these early trials to increase their chance of success. Here, we explore the evolution of FSHD clinical trials from nonspecific anabolic or anti-inflammatory/oxidant strategies to cutting-edge molecular therapies targeting DUX4, and we discuss the importance of clinical outcome measures. With combined advances across multiple facets of FSHD research, the field is now poised to accelerate the process of therapeutic discovery and testing.

Keywords: DUX4; anabolic; clinical outcome measures; clinical trials; facioscapulohumeral muscular dystrophy; therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Clinical Studies as Topic
  • Combined Modality Therapy
  • Disease Management
  • Disease Susceptibility
  • Drug Development
  • Drug Evaluation, Preclinical
  • Genetic Predisposition to Disease
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Muscular Dystrophy, Facioscapulohumeral / diagnosis
  • Muscular Dystrophy, Facioscapulohumeral / etiology
  • Muscular Dystrophy, Facioscapulohumeral / metabolism
  • Muscular Dystrophy, Facioscapulohumeral / therapy*
  • Oxidation-Reduction
  • Treatment Outcome

Substances

  • Biomarkers
  • DUX4L1 protein, human
  • Homeodomain Proteins