Hsp72 preserves muscle function and slows progression of severe muscular dystrophy

SM Gehrig; C Van Der Poel; TA Sayer; JD Schertzer; DC Henstridge; JE Church; S Lamon; AP Russell; KE Davies; MA Febbraio; GS Lynch

Journal article

Hsp72 preserves muscle function and slows progression of severe muscular dystrophy

SM Gehrig, C Van Der Poel, TA Sayer, JD Schertzer, DC Henstridge, JE Church, S Lamon, AP Russell, KE Davies, MA Febbraio, GS Lynch

Nature | NATURE PUBLISHING GROUP | Published : 2012

DOI: 10.1038/nature10980

Abstract

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca2+, which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in..

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Gordon Lynch Author

Tim Sayer Author

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Grants

Awarded by National Heart Foundation of Australia

Funding Acknowledgements

We thank R. Koopman, J. G. Ryall and G. I. Lancaster for comments; J. Trieu, B. G. Gleeson, T. Naim and A. Chee for technical support; and C. Angelini and the Neuromuscular bank of tissues and DNA samples - Telethon Network of Genetic Biobanks for the provision of human muscle specimens. We thank N-Gene R&D Inc. USA for providing the BGP-15 compound. This study was supported in part by research grants from the National Health and Medical Research Council (NHMRC; project numbers 1009114 to G. S. L. and 472650 and 1004441 to M.A.F.), Association Francaise contre les Myopathies (France, to G. S. L.) and the Muscular Dystrophy Association (USA, to G. S. L.). M. A. F. is a Senior Principal Research Fellow of the NHMRC. A. P. R. was supported by a NHMRC Biomedical career Development Award. S. L. was supported by a postdoctoral fellowship from the Swiss National Science Foundation. S. M. G. was supported by a National Heart Foundation Postgraduate Scholarship (Australia). D. C. H. was supported by a National Heart Foundation Post-Doctoral Fellowship.