The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice

Mol Ther. 2020 Jan 8;28(1):189-201. doi: 10.1016/j.ymthe.2019.08.016. Epub 2019 Sep 3.


Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease that is caused by the loss of functional dystrophin protein in cardiac and skeletal muscles. DMD patient muscles become weakened, leading to eventual myofiber breakdown and replacement with fibrotic and adipose tissues. Inflammation drives the pathogenic processes through releasing inflammatory cytokines and other factors that promote skeletal muscle degeneration and contributing to the loss of motor function. Selective inhibitors of nuclear export (SINEs) are a class of compounds that function by inhibiting the nuclear export protein exportin 1 (XPO1). The XPO1 protein is an important regulator of key inflammatory and neurological factors that drive inflammation and neurotoxicity in various neurological and neuromuscular diseases. Here, we demonstrate that SINE compound KPT-350 can ameliorate dystrophic-associated pathologies in the muscles of DMD models of zebrafish and mice. Thus, SINE compounds are a promising novel strategy for blocking dystrophic symptoms and could be used in combinatorial treatments for DMD.

Keywords: CRM1; DMD; KPT-350; SINE; XPO1; muscle inflammation; muscle zebrafish.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / drug effects*
  • Administration, Oral
  • Animals
  • Biomarkers / blood
  • Cytokines / antagonists & inhibitors
  • Cytokines / blood
  • Disease Models, Animal
  • Karyopherins / antagonists & inhibitors*
  • Locomotion / drug effects
  • Macrophages / drug effects
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred DBA
  • Mice, Inbred mdx
  • Muscle Proteins / genetics
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Mutation
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics


  • Biomarkers
  • Cytokines
  • Karyopherins
  • Membrane Proteins
  • Muscle Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Zebrafish Proteins
  • dmd protein, zebrafish
  • exportin 1 protein