Myostatin, is a type II activin receptor ACVR2B agonist. Myostatin-induced ACVR2B activation leads to SMAD pathway signalling.
Inhibition of Myostatin/ACVR2B signalling is a mechanistic target for the development of drugs to combat muscle wasting conditions. We list three clinical stage anti-myostatin monoclonal antibodies (mAbs) in the 'Biological activity' tab for this ligand. In addition to mAbs, alternative protein scaffolds are being investigated to produce anti-myostatin activity similar to mAbs but with simpler, single-domain structures and no disulfide bonds. One such example is talditercept alfa (RO7239361, BMS-986089), which is a fusion protein that derives myostatin-binding from a modified human fibronectin domain F10. Talditercept alfa has advanced to Phase 1/2 evaluation to reduce muscle atrophy in boys with Duchenne muscular dystrophy (NCT02515669
). Talditercept alfa is an example of so-called 'Adnectin' protein therapeutics that are being developed as an alternative to antigen receptors (antibodies) [5