Anti-myostatin: an effectiveness depending on the importance of the muscular damage

The team of J. Dumonceaux has shown that anti-myostatin therapy is effective if the level of myostatin is sufficient.

Anti-myostatin molecules inhibit the myostatin pathway: myostatin is a protein secreted by muscle that naturally inhibits muscle growth. Several therapeutic approaches aimed at increasing muscle mass and targeting myostatin have been studied in clinical trials. However, so far, the results have been inconclusive.

The team of J. Dumonceaux (London, United Kingdom) has studied the quantity of myostatin and the various molecules involved in the myostatin pathway in the blood and in muscle biopsies of patients with different neuromuscular diseases.

  • The results of this study, which were also presented at the 22nd International Congress of the World Muscle Society (Saint-Malo, October 3-7, 2017), showed that the more severe the muscle atrophy, as in Duchenne muscular dystrophy or SMN1-related proximal spinal muscular atrophy, the lower the level of myostatin, which may explain why anti-myostatin therapies have not been effective.


Muscle atrophy Level of myostatin
(in blood and muscle)
Duchenne Muscular Dystrophy (DMD) ++
SMN1-related proximal Spinal Muscular Atrophy (SMA) ++
Becker Muscular Dystrophy (BMD) + +
Facioscapulohumeral Dystrophy (FSH) + +
Inclusion-Body Myositis (IBM) + +
Myasthenia Gravis
(No atrophy)


  • The authors also observed that the myotubular myopathy mouse model, which does not express myotubularin and has generalised muscle atrophy, expresses very little myostatin. Treatment with anti-myostatin in this mouse model therefore did not increase its muscle mass.
    In contrast, the prior introduction of the myotubularin gene (via gene therapy) into these myotubularin-deficient mice increases their muscle mass and restores the expression of myostatin: mice are therefore susceptible to treatment with anti-myostatin which further increases their muscle mass.

The authors emphasised the importance of measuring myostatin levels in patients before starting a clinical trial with anti-myostatin.

Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches.Mariot V, Joubert R, Hourdé C, Féasson L, Hanna M, Muntoni F, Maisonobe T, Servais L, Bogni C, Le Panse R, Benvensite O, Stojkovic T, Machado PM, Voit T, Buj-Bello A, Dumonceaux J.Nat Commun., 2017 (Nov)