Production of specific myostatin antagonists
Myostatin/GDF8 is a negative regulator of skeletal muscle mass: high levels of myostatin activity are associated with muscular atrophy, cachexia, sarcopenia. Since loss or decrease of myostatin activity lead to significant increase in muscle mass, it is generally accepted that myostatin antagonists might be valuable for the treatment of muscle-wasting diseases.
Several natural proteins have been identified that bind myostatin and prevent its interaction with the myostatin receptor. Although follistatin, FSTL-3, WFIKKN1 and WFIKKN2 are potent myostatin antagonists, they also inhibit the activity of other members of the TGF-β family therefore their therapeutic application may have undesirable side effects. The most specific myostatin inhibitors derive from the prodomain region of promyostatin, however, their affinity for myostatin is relatively weak. The goal of the cooperation is to generate variants of the myostatin prodomain that are more potent antagonists of myostatin than the wild type protein.
László Patthy, András Perczel