Myostatin is a member of the
TGF-beta superfamily that is expressed predominantly in skeletal muscle and functions as a negative regulator of skeletal muscle mass.
Myostatin inhibition, therefore, has tremendous potential for increasing muscle mass clinically to treat patients with muscle
wasting diseases. Systemic administration of a
myostatin neutralizing antibody in mdx mice (a model of
Duchenne muscular dystrophy) resulted in an increase in skeletal muscle mass and strength. A human anti-
myostatin monoclonal antibody,
MYO-029 is under clinical trials in patients with
muscular dystrophy in the USA and Europe. Additional approaches to
myostatin inhibition have been shown to have beneficial effects in vivo. Blockade of
myostatin activity with the
myostatin prodomain resulted in increases in muscle mass, enhanced muscle function, and histological improvement of the dystrophic muscle in mdx mice and mutant
caveolin-3 transgenic mice (a model of
LGMD1C). Treatment with an extracellular
ligand-binding domain of the
myostatin receptor, ActRIIB, resulted in prominent muscle mass increases in
LGMD1C model mice. These findings indicate that
myostatin inhibition could lead to effective
therapeutics to treat
muscular dystrophy. However, therapeutic indication against various types of
muscular dystrophy as well as safety of the treatment should be established for the future clinical application.