Journal article
Using AAV vectors expressing the β 2 -adrenoceptor or associated Gα proteins to modulate skeletal muscle mass and muscle fibre size
A Hagg, TD Colgan, RE Thomson, H Qian, GS Lynch, P Gregorevic
Scientific Reports | Published : 2016
DOI: 10.1038/srep23042
Abstract
Anabolic β 2 -adrenoceptor (β 2 -AR) agonists have been proposed as therapeutics for treating muscle wasting but concerns regarding possible off-target effects have hampered their use. We investigated whether β 2 -AR-mediated signalling could be modulated in skeletal muscle via gene delivery to the target tissue, thereby avoiding the risks of β 2 -AR agonists. In mice, intramuscular administration of a recombinant adeno-associated virus-based vector (rAAV vector) expressing the β 2 -AR increased muscle mass by >20% within 4 weeks. This hypertrophic response was comparable to that of 4 weeks treatment with the β 2 -AR agonist formoterol, and was not ablated by mTOR inhibition. Increasing expr..
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Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
The authors thank Dr Catherine E. Winbanks and Dr Lucy Cassar (previously Baker IDI Heart and Diabetes Institute), Mr Timur Naim (Department of Physiology, University of Melbourne) and Mr Stephen Cody and Dr Iska Carmichael (Micro Imaging facility, AMREP campus) for technical guidance. This work was supported by Project Grant funding (509313; 1026231 awarded to G.S.L. and P.G.) from the National Health and Medical Research Council (NHMRC). P.G. is supported by a NHMRC Career Development Fellowship (1046782) and previously, a Senior Research Fellowship sponsored by Pfizer Australia. The Baker IDI Heart & Diabetes Institute is supported in part by the Operational Infrastructure Support Program of the Victorian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.