Oculopharyngeal muscular dystrophy: potential therapies for an aggregate-associated disorder

Int J Biochem Cell Biol. 2006;38(9):1457-62. doi: 10.1016/j.biocel.2006.01.016. Epub 2006 Feb 28.

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, autosomal dominant disease caused by the abnormal expansion of a polyalanine tract within the coding region of poly(A) binding protein nuclear 1 (PABPN1). The resultant mutant PABPN1 forms aggregates within the nuclei of skeletal muscle fibres. The mechanism by which the polyalanine expansion mutation in PABN1 causes disease is unclear. However, the mutation is thought to confer a toxic gain-of-function on the protein. Despite controversy over the role of aggregates, it has been consistently shown that agents that reduce aggregate load in cell models of OPMD also reduce levels of cell death. Recently generated animal models of OPMD will help elucidate the mechanism of disease and allow the trial of potential therapeutics. Indeed, administration of known anti-aggregation drugs attenuated muscle weakness in an OPMD mouse model. This suggests that anti-aggregation therapies may be beneficial in OPMD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Doxycycline / therapeutic use
  • Humans
  • Inclusion Bodies / metabolism
  • Muscular Dystrophy, Oculopharyngeal / drug therapy*
  • Muscular Dystrophy, Oculopharyngeal / genetics
  • Peptides / metabolism
  • Poly(A)-Binding Protein II / genetics*
  • Protein Structure, Tertiary
  • Trehalose / therapeutic use
  • Trinucleotide Repeats

Substances

  • Peptides
  • Poly(A)-Binding Protein II
  • polyalanine
  • Trehalose
  • Doxycycline