Halofuginone prevents subglottic stenosis in a canine model.
OBJECTIVE
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.
Eliashar
Ron
R
Department of Otolaryngology-Head and Neck Surgery, The Hebrew University School of Medicine, Hadassah Medical Center, Jerusalem, Israel.
Ochana
Meir
M
Maly
Bella
B
Pines
Mark
M
Sichel
Jean-Yves
JY
Nagler
Arnon
A
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D066298:In Vitro Techniques; D007829:Laryngostenosis / Q000473:pathology / Q000517:prevention & control*; D016685:Mitomycin / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010880:Piperidines; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones; D016896:Treatment Outcome
D019384:Nucleic Acid Synthesis Inhibitors; D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D016685:Mitomycin; C010176:halofuginone