Myostatin is a protein in muscle cells that controls muscle growth. Reducing myostatin causes the growth of pre-existing muscle cells, enlarging the muscle fibers. When myostatin is reduced in healthy animals, muscles grow significantly larger. One example of this effect is Belgian Blue cattle, which genetically lack myostatin and have visibly more muscle and less fat than average cattle.  Drugs that reduce myostatin could potentially increase muscle mass in patients with muscular dystrophies to help them compensate for lost muscle mass that results in progressive weakness. In fact, researchers have previously discovered that reducing myostatin improves muscle mass and function in a mouse model of Duchenne muscular dystrophy, which is caused by missing the protein dystrophin. Dystrophin is thought to maintain the connection between the muscle cell membrane and the surrounding tissue.


In their article Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy, the researchers investigated whether reducing myostatin on mice lacking dysferlin was beneficial as it was in mice lacking dystrophin. Dysferlin-deficient mice are a model for LGMD2B or Miyoshi Myopathy—collectively called dysferlinopathy. In this article, researchers used two different methods to remove or reduce myostatin from mice that lack dysferlin. First, they added the protein follistatin, which blocks myostatin function. The results initially showed the desired increase in mass, but also identified some long-term concerns. Instead of maintaining the extra muscle gained early in the experiment, animals began to rapidly lose muscle and the researchers noticed abnormalities within the muscle cells, reduced force of contraction, and greater damage to the muscle cells (measured by elevated CK levels). The drug activin receptor II, which reduces the effect of myostatin, had a less dramatic impact on muscle growth initially and also a less pronounced drop in muscle mass later, but there were still issues such as increased muscle damage. Immune system activation was observed following both activin and follistatin treatment, further indicating damage. A possible explanation is that reducing myostatin increases the size of the fibers, increasing stress on the individual muscle fibers, which are already susceptible to damage.


The results show that reducing myostatin has potent muscle building effects in muscular dystrophies, but may also have long-term treatment concerns for dysferlinopathy. The potential benefits of reducing myostatin need to be weight against the dangers to determine if reducing myostatin in various ways might be a possible therapy to help LGMD2B/MM patients. It also isn’t clear whether dysferlin deficiency is unique in its apparent lack of tolerance for myostatin inhibition, or dystrophin deficiency is unique in benefitting from the therapy.