Journal article
Development of novel activin-targeted therapeutics
JL Chen, KL Walton, SL Al-Musawi, EK Kelly, H Qian, M La, L Lu, G Lovrecz, M Ziemann, R Lazarus, A El-Osta, P Gregorevic, CA Harrison
Molecular Therapy | CELL PRESS | Published : 2015
DOI: 10.1038/mt.2014.221
Abstract
Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-β proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, "fastener" residues (Lys45, Tyr96, His97, and Ala98; activin A numbering) that confer lat..
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Awarded by State Government of Victoria
Funding Acknowledgements
Myostatin-null mice were a gift of Se-Jin Lee (Johns Hopkins University, Baltimore, MD). This work was supported by grant funding (526648, 566820) from the National Health and Medical Research Council (NH&MRC, Australia). CAH and PG are supported by NH&MRC Career Development Fellowships (1013533, 1046782 respectively). P.G. was previously supported by a Senior Research Fellowship sponsored by Pfizer Australia. An Endocrine Society of Australia Postdoctoral Fellowship Award supports K.L.W. MIMR-PHI Institute of Medical Research and The Baker IDI Heart & Diabetes Institute are supported in part by the Operational Infrastructure Support Program of the Victorian Government, Australia. The authors declare no conflict of interest.