Using AAV vectors expressing the beta 2-adrenoceptor or associated G alpha proteins to modulate skeletal muscle mass and muscle fibre size
Adam Hagg, Timothy D Colgan, Rachel E Thomson, Hongwei Qian, Gordon S Lynch, Paul Gregorevic
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2016
Anabolic β2-adrenoceptor (β2-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 β2-AR-mediated signalling could be modulated in skeletal muscle via gene delivery to the target tissue, thereby avoiding the risks of β2-AR agonists. In mice, intramuscular administration of a recombinant adeno-associated virus-based vector (rAAV vector) expressing the β2-AR increased muscle mass by >20% within 4 weeks. This hypertrophic response was comparable to that of 4 weeks' treatment with the β2-AR agonist formoterol, and was not ablated by mTOR inhibition. Increasing expression of i..View full abstract
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Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NHMRC
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.