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

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.

Type Journal
ISBN 1525-2191 (Electronic) 0002-9440 (Linking)
Authors Kennedy, T. L.; Swiderski, K.; Murphy, K. T.; Gehrig, S. M.; Curl, C. L.; Chandramouli, C.; Febbraio, M. A.; Delbridge, L. M.; Koopman, R.; Lynch, G. S.;
Publisher Name AM J PATHOL
Published Date 2016-01-01 00:00:00
Published Volume 186
Published Issue 12
Published Pages 3246-3260
URL http://www.ncbi.nlm.nih.gov/pubmed/27750047
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?13789_13595/2016-Kennedy-Am J Pathol.pdf