The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle

Cells. 2020 Dec 10;9(12):2657. doi: 10.3390/cells9122657.


Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcome measures selected: the myostatin inhibition story, thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models have failed to translate into clinical benefit to patients have been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.

Keywords: Duchenne Muscular Dystrophy; clinical trials; muscle development; myostatin inhibition; skeletal muscle; translation.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antibodies / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Mice
  • Muscle, Skeletal / drug effects
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / genetics
  • Myostatin / antagonists & inhibitors*
  • Treatment Failure


  • Antibodies
  • MSTN protein, human
  • Myostatin