An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

• DOI: 10.1128/mcb.01307-13
• Publication Date: 2013-12-03T03:15:09Z
• Authors: Estelle Lach-Trif...; Giulia C. Minetti; KellyAnn Sheppard; Chikwendu Ibebunjo; Jerome N. Feige; Steffen Hartmann; Sophie Brachat; Helene Rivet; Claudia Koelbing; Frederic Morvan; Shinji Hatakeyama; David J. Glass
• Keywords: Myostatin; Activin receptor; Smad2 Protein; ACVR2B; Muscle Atrophy

The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that ActRII receptors are major regulatory nodes regulation of mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) prevent binding ligands thus inhibit downstream signaling. BYM338 enhances differentiation primary myoblasts counteracts inhibition induced by myostatin activin A. prevents myostatin- A-induced atrophy Smad2/3 phosphorylation, sparing myosin heavy chain from degradation. dramatically increases mass mice, beyond sole myostatin, detected comparing with inhibitor. A mouse version induces enhanced hypertrophy mutant further confirming beneficial effect on growth alone blockade ligands. protects muscles glucocorticoid-induced weakness via prevention tetanic force losses. These data highlight compelling therapeutic potential for treatment multiple settings.