Blocking extracellular activation of myostatin as a strategy for treating muscle wasting.

ABSTRACT: Many growth factors are intimately bound to the extracellular matrix, with regulated processing and release leading to cellular stimulation. Myostatin and GDF11 are closely related members of the TGFβ family whose activation requires two proteolytic cleavages to release the growth factor from the prodomain. Specific modulation of myostatin and GDF11 activity by targeting growth factor-receptor interactions has traditionally been challenging. Here we demonstrate that a novel strategy for blocking myostatin and GDF11, inhibition of growth factor release, specifically and potently inhibits signaling both in vitro and in vivo. We developed human monoclonal antibodies that selectively bind the myostatin and GDF11 precursor forms, including a subset that inhibit myostatin proteolytic activation

SUBMITTER: Pirruccello-Straub M 

PROVIDER: S-EPMC5797207 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature