Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammatory disorders

Abstract

A survey of the available biological data on tryptase inhibitors suggests that there is considerable interest in tryptase as a therapeutic target particularly for the treatment of allergic asthma and inflammatory disorders. This interest was driven primarily by data from studies carried out on the cellular and in vivo actions of this serine protease over the past decade, all of which have suggested a pro-inflammatory role for tryptase. Tryptase beta is the form of interest in allergic asthma and the data from numerous studies have shown that tryptase cannot only contribute to airway bronchoconstriction and hyperresponsiveness, but may have a key role in fibrosis and ECM turnover, hallmarks of the remodeling process. Hence, inhibitors of tryptase have the potential to make an impact on fibrosis and airway wall remodelling. However, few studies, if any, have been carried out to determine the effect of tryptase inhibitors on airway remodeling and this is an area that warrants further investigation with the appropriate models because the eventual positioning of tryptase inhibitors in asthma therapy will be strengthened by data supporting an impact on airway remodeling in addition to effects on bronchial hyperresponsiveness. This review has focused on tryptase inhibitors in the pipeline and it is clear that with a few exceptions, the majority of these compounds are targeted for inhaled delivery. Finally, judging by the interest from numerous pharmaceutical companies, it appears the stage is set for tryptase inhibitors to make their mark as drugs of the future for allergic asthma and the results from clinical trials is awaited with eager anticipation.