Spinal and bulbar muscular atrophy: From molecular pathogenesis to pharmacological intervention targeting skeletal muscle

Curr Opin Pharmacol. 2023 Aug:71:102394. doi: 10.1016/j.coph.2023.102394. Epub 2023 Jul 16.

Abstract

The clinical characteristics of SBMA, also known as Kennedy's disease (OMIM 313200), were initially documented by Dr. H Kawahara in the 18th century and a hundred years later by Dr. W. Kennedy. SBMA is a neuromuscular disease caused by expansions of a CAG microsatellite tandem repeat in exon 1 of the androgen receptor (AR) gene located on the X chromosome. These expansions result in the production of AR with an aberrantly expanded polyglutamine (polyQ) tract. In this review, we explore recent advancements in the significance of gene expression changes in skeletal muscle and discuss how pharmacological interventions targeting this aspect of disease pathogenesis can potentially be translated into therapies for SBMA patients.

Publication types

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

MeSH terms

  • Bulbo-Spinal Atrophy, X-Linked* / drug therapy
  • Bulbo-Spinal Atrophy, X-Linked* / genetics
  • Bulbo-Spinal Atrophy, X-Linked* / metabolism
  • Humans
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Receptors, Androgen / therapeutic use

Substances

  • Receptors, Androgen