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Article Dans Une Revue Nature Communications Année : 2017

Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches

Virginie Mariot
  • Fonction : Auteur
Romain Joubert
Christophe Hourdé
  • Fonction : Auteur
Léonard Féasson
Michael Hanna
  • Fonction : Auteur
Francesco Muntoni
  • Fonction : Auteur
Thierry Maisonobe
  • Fonction : Auteur
Laurent Servais
  • Fonction : Auteur
Caroline Bogni
  • Fonction : Auteur
Rozen Le Panse
  • Fonction : Auteur
Olivier Benvensite
  • Fonction : Auteur
Tanya Stojkovic
  • Fonction : Auteur
Pedro Machado
Thomas Voit
  • Fonction : Auteur
Julie Dumonceaux
  • Fonction : Auteur

Résumé

Abstract Muscular dystrophies are characterized by weakness and wasting of skeletal muscle tissues. Several drugs targeting the myostatin pathway have been used in clinical trials to increase muscle mass and function but most showed limited efficacy. Here we show that the expression of components of the myostatin signaling pathway is downregulated in muscle wasting or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the myostatin antagonist, follistatin. We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding gene Mtm1 ) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene defect. Our data may explain the poor clinical efficacy of anti-myostatin approaches in several of the clinical studies and the apparent contradictory results in mice regarding the efficacy of anti-myostatin approaches and may inform patient selection and stratification for future trials.

Dates et versions

hal-04481602 , version 1 (28-02-2024)

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Citer

Virginie Mariot, Romain Joubert, Christophe Hourdé, Léonard Féasson, Michael Hanna, et al.. Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches. Nature Communications, 2017, 8 (1), pp.1859. ⟨10.1038/s41467-017-01486-4⟩. ⟨hal-04481602⟩
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