Activin IIB receptor blockade attenuates dystrophic pathology in a mouse model of duchenne muscular dystrophy

Kevin J. Morine, Lawrence T. Bish, Joshua T. Selsby, Jeffery A. Gazzara, Klara Pendrak, Meg M. Sleeper, Elisabeth R. Barton, Se Jin Lee, H. Lee Sweeney

Research output: Contribution to journalArticle

Abstract

Modulation of transforming growth factor-β (TGF-β) signaling to promote muscle growth holds tremendous promise for the muscular dystrophies and other disorders involving the loss of functional muscle mass. Previous studies have focused on the TGF-β family member myostatin and demonstrated that inhibition of myostatin leads to muscle growth in normal and dystrophic mice. We describe a unique method of systemic inhibition of activin IIB receptor signaling via adeno-associated virus (AAV)-mediated gene transfer of a soluble form of the extracellular domain of the activin IIB receptor to the liver. Treatment of mdx mice with activin IIB receptor blockade led to increased skeletal muscle mass, increased force production in the extensor digitorum longus (EDL), and reduced serum creatine kinase. No effect on heart mass or function was observed. Our results indicate that activin IIB receptor blockade represents a novel and effective therapeutic strategy for the muscular dystrophies.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalMuscle and Nerve
Volume42
Issue number5
DOIs
StatePublished - Nov 1 2010

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Keywords

  • Activin IIB receptor
  • Adenoassociated virus
  • Gene therapy
  • Muscular dystrophy
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Morine, K. J., Bish, L. T., Selsby, J. T., Gazzara, J. A., Pendrak, K., Sleeper, M. M., Barton, E. R., Lee, S. J., & Sweeney, H. L. (2010). Activin IIB receptor blockade attenuates dystrophic pathology in a mouse model of duchenne muscular dystrophy. Muscle and Nerve, 42(5), 722-730. https://doi.org/10.1002/mus.21743