Fibrosis inhibition and muscle histopathology improvement in laminin-α2-deficient mice

Yoram Nevo, Orna Halevy, Olga Genin, Itai Moshe, Tidhar Turgeman, Michal Harel, Edva Biton, Shimon Reif, Mark Pines*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In muscular dystrophies (MD) the loss of muscle and its ability to function are associated with fibrosis. We evaluated the efficacy of halofuginone in reducing fibrosis in the dy2J/dy2J mouse model of congenital MD. Mice were injected intraperitoneally with 5 μg of halofuginone 3 times a week for 5 or 15 weeks, starting at the age of 3 weeks. Halofuginone caused a reduction in collagen synthesis in hindlimb muscles. This was associated with reductions in the degenerated area, in cell proliferation, in the number of myofibers with central nuclei, with increased myofiber diameter, and with enhanced motor coordination and balance. Halofuginone caused a reduction in infiltrating fibroblasts that were located close to centrally nucleated myofibers. Our results suggest that halofuginone reduced the deleterious effects of fibrosis, thus improving muscle integrity. Halofuginone meets the criteria for a novel antifibrotic therapy for MD patients.

Original languageEnglish
Pages (from-to)218-229
Number of pages12
JournalMuscle and Nerve
Volume42
Issue number2
DOIs
StatePublished - Aug 2010
Externally publishedYes

Keywords

  • Collagen
  • Fibrosis
  • Halofuginone
  • Prolyl 4 hydroxylase
  • Smad3

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