Halofuginone prevents subglottic stenosis in a canine model

Ron Eliashar, Meir Ochana, Bella Maly, Mark Pines, Jean Yves Sichel, Arnon Nagler

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Halofuginone is a low-molecular weight quinazolinone alkaloid coccidiostat that inhibits collagen type I synthesis, extracellular matrix deposition, and angiogenesis. This study was conducted to assess its potential in preventing subglottic stenosis (SGS). Methods: We induced SGS in 10 dogs randomly divided into 2 groups. Each group received treatment between 3 days before and 21 days after the induction of SGS. One group received oral halofuginone 40 μg/kg, and the other was given placebo. The area of the subglottic lumen was measured at baseline and 3 months later. In addition, human tracheal fibroblasts were cultured. The inhibitory effect of halofuginone was compared to the effect of mitomycin. Results: All dogs survived throughout the study with no side effects. Three months after the operation, no halofuginone-treated dog had SGS, in contrast to a 66% to 80% stenosis rate (mean, 72%) in controls (p < .008). Thick fibrotic tissue was found in the placebo-treated larynges, whereas an almost normal architecture was observed in halofuginone-treated larynges. Halofuginone inhibited the growth of human tracheal fibroblasts by 75%, in comparison with 60% inhibition by mitomycin (no statistically significant difference). Conclusions: This preliminary study shows that halofuginone is effective in preventing SGS caused by an acute injury. Halofuginone has a potential therapeutic role in preventing SGS in humans.

Original languageEnglish
Pages (from-to)382-386
Number of pages5
JournalAnnals of Otology, Rhinology and Laryngology
Volume115
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Keywords

  • Halofuginone
  • Larynx
  • Mitomycin
  • Stenosis
  • Subglottic stenosis
  • Wound healing

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