Smad7 gene delivery prevents muscle wasting associated with cancer cachexia in mice

CE Winbanks; KT Murphy; BC Bernardo; H Qian; Y Liu; PV Sepulveda; C Beyer; A Hagg; RE Thomson; JL Chen; KL Walton; KL Loveland; JR McMullen; BD Rodgers; CA Harrison; GS Lynch; P Gregorevic

Journal article

Smad7 gene delivery prevents muscle wasting associated with cancer cachexia in mice

CE Winbanks, KT Murphy, BC Bernardo, H Qian, Y Liu, PV Sepulveda, C Beyer, A Hagg, RE Thomson, JL Chen, KL Walton, KL Loveland, JR McMullen, BD Rodgers, CA Harrison, GS Lynch, P Gregorevic

Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2016

DOI: 10.1126/scitranslmed.aac4976

Abstract

Patients with advanced cancer often succumb to complications arising from striated muscle wasting associated with cachexia. Excessive activation of the type IIB activin receptor (ActRIIB) is considered an important mechanism underlying this wasting, where circulating procachectic factors bind ActRIIB and ultimately lead to the phosphorylation of SMAD2/3. Therapeutics that antagonize the binding of ActRIIB ligands are in clinical development, but concerns exist about achieving efficacy without off-target effects. To protect striated muscle from harmful ActRIIB signaling, and to reduce the risk of off-target effects, we developed an intervention using recombinant adeno-associated viral vectors..

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University of Melbourne Researchers

Bianca Bernardo Author

Hongwei Qian Author

Rachel Thomson Author

Julie McMullen Author

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Grants

Awarded by National Science Foundation

Funding Acknowledgements

This work was supported by grant funding (526648 and 566820) from the National Health and Medical Research Council (NHMRC, Australia). J.R.M. is supported by a Senior Research Fellowship (1078985) from NHMRC. K.T.M., C.A.H., and P.G. are supported by Career Development Fellowships (1023178, 1013533, and 1046782, respectively) from NHMRC. B.D.R. is supported by the National Science Foundation (NSF, USA; IOS1147275) and the Muscular Dystrophy Association (USA). The Baker IDI Heart and Diabetes Institute is supported in part by the Operational Infrastructure Support Program of the Victorian Government, Australia.