Sunitinib promotes myogenic regeneration and mitigates disease progression in the mdx mouse model of Duchenne muscular dystrophy

Hum Mol Genet. 2019 Jul 1;28(13):2120-2132. doi: 10.1093/hmg/ddz044.


Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD is characterized by mutations in the dystrophin gene that result in a loss of the dystrophin protein. Loss of dystrophin causes an associated reduction in proteins of the dystrophin glycoprotein complex, leading to contraction-induced sarcolemmal weakening, muscle tearing, fibrotic infiltration and rounds of degeneration and failed regeneration affecting satellite cell populations. The α7β1 integrin has been implicated in increasing myogenic capacity of satellite cells, therefore restoring muscle viability, increasing muscle force and preserving muscle function in dystrophic mouse models. In this study, we show that a Food and Drug Administration (FDA)-approved small molecule, Sunitinib, is a potent α7 integrin enhancer capable of promoting myogenic regeneration by stimulating satellite cell activation and increasing myofiber fusion. Sunitinib exerts its regenerative effects via transient inhibition of SHP-2 and subsequent activation of the STAT3 pathway. Treatment of mdx mice with Sunitinib demonstrated decreased membrane leakiness and damage owing to myofiber regeneration and enhanced support at the extracellular matrix. The decreased myofiber damage translated into a significant increase in muscle force production. This study identifies an already FDA-approved compound, Sunitinib, as a possible DMD therapeutic with the potential to treat other muscular dystrophies in which there is defective muscle repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Disease Models, Animal
  • Disease Progression
  • Integrins / metabolism
  • Male
  • Mice
  • Mice, Inbred mdx
  • Muscle Development / drug effects
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / drug therapy*
  • MyoD Protein / metabolism
  • Myoblasts / cytology
  • Myoblasts / drug effects*
  • Myoblasts / metabolism
  • Myogenin / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / drug effects
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Regeneration
  • STAT3 Transcription Factor / drug effects
  • STAT3 Transcription Factor / metabolism
  • Satellite Cells, Skeletal Muscle / drug effects
  • Satellite Cells, Skeletal Muscle / metabolism
  • Sunitinib / pharmacology
  • Sunitinib / therapeutic use*


  • Integrins
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Myogenin
  • STAT3 Transcription Factor
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Ptpn6 protein, mouse
  • integrin alpha7beta1
  • Sunitinib