Halofuginone prevents subglottic stenosis in a canine model

Ann Otol Rhinol Laryngol. 2006 May;115(5):382-6. doi: 10.1177/000348940611500511.

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 microg/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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cells, Cultured
  • Disease Models, Animal
  • Dogs
  • Fibroblasts / drug effects
  • Fibroblasts / pathology
  • Follow-Up Studies
  • Humans
  • In Vitro Techniques
  • Laryngostenosis / pathology
  • Laryngostenosis / prevention & control*
  • Mitomycin / pharmacology
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Piperidines
  • Protein Synthesis Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*
  • Quinazolinones
  • Treatment Outcome

Substances

  • Nucleic Acid Synthesis Inhibitors
  • Piperidines
  • Protein Synthesis Inhibitors
  • Quinazolines
  • Quinazolinones
  • Mitomycin
  • halofuginone