Tryptase inhibition

Tryptase, a mast-cell-specific serine protease, has been used for a number of years as a marker of mast cell activation. Elevated levels of the enzyme have been detected in allergic diseases including asthma, conjunctivitis a nd rhinitis, and in some diseases in which mast cell mediators have been hy pothesized to play a role, such as rheumatoid arthritis, inflammatory bowel disease and interstitial cystitis. In the case of asthma, numerous studies suggested a role for tryptase in the underlying pathology of the disease. APC 366, a small molecule inhibitor of tryptase, has shown efficacy in vivo , thus confirming a causal role for tryptase in experimental models of alle rgic asthma. In recent phase II clinical trials, APC 366 has demonstrated e fficacy in patients with mild to moderate asthma. Together, these data prov ide a compelling rationale for the development of tryptase inhibitors with greater potency and selectivity for the treatment of asthma and other aller gic diseases.