title: 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.
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Tahnee L
authors.initials: TL
authors.lastname: Kennedy
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Kristy
authors.initials: K
authors.lastname: Swiderski
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Kate T
authors.initials: KT
authors.lastname: Murphy
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Gehrig
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Curl
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Chanchal
authors.initials: C
authors.lastname: Chandramouli
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: Cardiac Phenomics Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria.
authors.forename: René
authors.initials: R
authors.lastname: Koopman
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Melbourne, Victoria. Electronic address: gsl@unimelb.edu.au.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000503:physiopathology; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D010091:Oximes / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D049411:Utrophin / Q000235:genetics* / Q000378:metabolism
chemical_list: D016189:Dystrophin; D050884:HSP72 Heat-Shock Proteins; D010091:Oximes; D010880:Piperidines; D049411:Utrophin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C405586:BGP 15