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Fidarestat Decrease Allergic Sinus Congestion
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Walter C. Spear, M.Sc., KarryAnne K. Belanger, B.Sc., Spotswood Miller, B.Sc., Igor Patrikeev, Ph.D, Massoud Motamedi, PhD, Kota V Ramana, Ph.D., Satish Srivastava, Ph.D., Bill T. Ameredes, PhD
Rationale: Sinus congestion and increased difficulty breathing are symptoms of allergic upper airway inflammation, requiring drug treatment to mitigate their effects. While steroids are effective, development of non-steroidal alternatives are desirable to offer additional options for therapy. An aldose reductase inhibitor, Fidarestat (FID), has been shown to have anti-inflammatory properties, and therefore was evaluated in a guinea pig (GP) model, which has relevant allergic similarities to humans. Fluticasone, a commonly-used anti-inflammatory steroid, was utilized as a comparator.
Methods: GPs were administered ragweed pollen (RWP; 20µg intranasally; i.n.) once per day, for 5 days, to induce allergic airway inflammation, against which the effects of i.n. FID (0-1.0%) and Fluticasone (50-100 mcg) were compared by measurements of sinus fill volume (SFV), as an index of sinus congestion. Statistical comparisons of SFV were assessed by t-tests.
Results: As compared to naïve GPs, RWP significantly increased allergic sinus congestion (as decreased SFV) by over 80% (P<0.05), which was subsequently reversed by Fluticasone to levels not statistically different from the naïve group. FID also increased SFV (and therefore reduced sinus congestion) toward the naïve level, in a concentration-dependent fashion, with SFV at the highest concentrations of FID being not different from the naïve or Fluticasone groups.
Conclusions: These results indicate that FID can effectively reduce allergic sinus congestion by magnitudes similar to an anti-inflammatory steroid, in a human-relevant guinea pig model of allergic rhinitis. Therefore, we conclude that intranasal FID may be a desirable candidate for therapeutic development in the treatment of allergic sinus inflammation and congestion.