Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy

Janet E Davies, Sovan Sarkar, David C Rubinsztein

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147 Citations (Scopus)


Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that presents in the fifth or sixth decade with dysphagia, ptosis and proximal limb weakness. OPMD is caused by the abnormal expansion of a polyalanine tract within the coding region of polyA binding protein nuclear 1 (PABPN1). The resultant mutant PABPN1 forms aggregates within the nuclei of skeletal muscle fibres. We have previously described a transgenic mouse model of OPMD that recapitulates the human disease and develops progressive muscle weakness accompanied by the formation of aggregates in skeletal muscle nuclei. The chemical chaperone trehalose has been used effectively to alleviate symptoms in a mouse model of Huntington's disease and is thought to elicit its effect by binding and stabilizing partially folded polyglutamine proteins and inhibiting the formation of aggregates. Here, we show that trehalose reduces aggregate formation and toxicity of mutant PABPN1 in cell models. Furthermore, oral administration of trehalose attenuated muscle weakness, reduced aggregate formation and decreased the number of TUNEL-labelled nuclei in skeletal muscle in an OPMD transgenic mouse model. Thus, anti-aggregation therapy may prove effective in the treatment of human OPMD.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalHuman Molecular Genetics
Issue number1
Publication statusPublished - 1 Jan 2006


  • Analysis of Variance
  • Animals
  • Blotting, Western
  • COS Cells
  • Cercopithecus aethiops
  • In Situ Nick-End Labeling
  • Inclusion Bodies
  • Mice
  • Mice, Transgenic
  • Muscle Contraction
  • Muscle, Skeletal
  • Muscular Dystrophy, Oculopharyngeal
  • Mutation
  • Poly(A)-Binding Protein II
  • Trehalose


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