BGP-15 Improves Aspects of the Dystrophic Pathology in mdx and dko Mice with Differing Efficacies in Heart and Skeletal Muscle

  • Am J Pathol. 2016 Dec;186(12):3246-3260. doi: 10.1016/j.ajpath.2016.08.008.
Tahnee L Kennedy  1 ,  Kristy Swiderski  1 ,  Kate T Murphy  1 ,  Stefan M Gehrig  1 ,  Claire L Curl  2 ,  Chanchal Chandramouli  2 ,  Mark A Febbraio  3 ,  Lea M D Delbridge  2 ,  René Koopman  1 ,  Gordon S Lynch  4
Affiliations
  • 1. Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
  • 2. Cardiac Phenomics Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
  • 3. Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • 4. Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria. Electronic address: [email protected].
PMID: 27750047 DOI: 10.1016/j.ajpath.2016.08.008
Abstract

Duchenne muscular dystrophy is a severe and progressive striated muscle wasting disorder that leads to premature death from respiratory and/or cardiac failure. We have previously shown that treatment of young dystrophic mdx and Dystrophin/utrophin null (dko) mice with BGP-15, a coinducer of heat shock protein 72, ameliorated the dystrophic pathology. We therefore tested the hypothesis that later-stage BGP-15 treatment would similarly benefit older mdx and dko mice when the dystrophic pathology was already well established. Later stage treatment of mdx or dko mice with BGP-15 did not improve maximal force of tibialis anterior (TA) muscles (in situ) or diaphragm muscle strips (in vitro). However, Collagen deposition (fibrosis) was reduced in TA muscles of BGP-15-treated dko mice but unchanged in TA muscles of treated mdx mice and diaphragm of treated mdx and dko mice. We also examined whether BGP-15 treatment could ameliorate aspects of the cardiac pathology, and in young dko mice it reduced Collagen deposition and improved both membrane integrity and systolic function. These results confirm BGP-15's ability to improve aspects of the dystrophic pathology but with differing efficacies in heart and skeletal muscles at different stages of the disease progression. These findings support a role for BGP-15 among a suite of pharmacological therapies for Duchenne muscular dystrophy and related disorders.

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