In the past 20 years, myostatin, a negative regulator of muscle mass, has attracted attention as a potential therapeutic target in muscular dystrophies and other conditions. Preclinical studies have shown potential for increasing muscular mass and ameliorating the pathological features of dystrophic muscle by the inhibition of myostatin in various ways. However, hardly any clinical trials have proven to translate the promising results from the animal models into patient populations. We present the background for myostatin regulation, clinical and preclinical results and discuss why translation from animal models to patients is difficult. Based on this, we put the clinical relevance of future antimyostatin treatment into perspective.

Muscular dystrophies constitute a broad group of genetic disorders leading to muscle wasting. We have previously demonstrated that treating a muscular atrophy mouse model with growth factors resulted in increased muscle mass. In the present study, we treated the Duchenne mouse model mdx for 12 weeks with myogenic growth factors peri- and post-onset of muscular degeneration to explore the effects in the oxidative muscle soleus and the glycolytic muscle extensor digitorum longus (EDL). We found no overall beneficial effect in the peri-onset group at the conclusion of the study. In the post-onset group, the functional improvement by means of electrophysiological examinations ex vivo was mostly confined to the soleus. EDL benefitted from the treatment on a molecular level but did not improve functionally. Histopathology revealed signs of inflammation at the end of treatment. In conclusion, the growth factor cocktail failed to improve the mdx on a functional level.