Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy
Copyright policy )Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy
Significance We recently reported that activin type II receptors (ActRIIs) blockade using bimagrumab could positively impact muscle wasting in mice and humans. However, the specific role of each individual ActRII at regulating adult muscle mass had not been clarified. Here, we highlight the importance of concomitant neutralization of both ActRIIs in controlling muscle mass. Through comparison with single specificity antibodies, we uncover unique features related to bimagrumab and its neutralizing interactions with both ActRIIA and ActRIIB at the structural and cellular levels and in vivo in adult mice. The need for simultaneous engagement and neutralization of both ActRIIs to generate a strong skeletal muscle response confers unique therapeutic potential to bimagrumab, in the context of muscle wasting conditions.
- Novartis Institutes for BioMedical Research Switzerland
- Novartis (Switzerland) Switzerland
- MorphoSys (Germany) Germany
Male, Activin Receptors, Type II, Mice, SCID, Antibodies, Monoclonal, Humanized, Crystallography, X-Ray, Mice, Animals, Humans, Rats, Wistar, Antibodies, Blocking, Muscle, Skeletal, Dose-Response Relationship, Drug, Antibodies, Monoclonal, Hypertrophy, Biological Sciences, Myostatin, Activins, Rats, Growth Differentiation Factors, HEK293 Cells, Bone Morphogenetic Proteins
Male, Activin Receptors, Type II, Mice, SCID, Antibodies, Monoclonal, Humanized, Crystallography, X-Ray, Mice, Animals, Humans, Rats, Wistar, Antibodies, Blocking, Muscle, Skeletal, Dose-Response Relationship, Drug, Antibodies, Monoclonal, Hypertrophy, Biological Sciences, Myostatin, Activins, Rats, Growth Differentiation Factors, HEK293 Cells, Bone Morphogenetic Proteins
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