Another Angle On Asthma; Arris Pharmaceuticals

Last month, Arris Pharmaceutical presented positive results from a Phase IIa trial of its tryptase inhibitor APC-366 in patients with asthma (Marketletter May 6). This study is thought to be the first time that a tryptase inhibitor has been tested clinically in this indication. The following article examines the scientific evidence for the role of tryptase in asthma, takes a closer look at the clinical data and reports Arris' plans for the future development of the drug.

Scientists working in asthma research have yet to reach a consensus on the relative importance of eosinophils and mast cells in bronchial asthma. New insights into the role of mast cell tryptase in the mediation of bronchoconstriction and inflammation in the asthmatic lung, presented at the American Lung Association meeting in New Orleans, lend further weight to the arguments of those who feel these cells are central to the pathology of the disease.

The Rationale Mast cell tryptase is a member of the large family of serine protease enzymes, which include elastase, trypsin and cathepsin G, which have long been associated with the tissue damage associated with asthma. Traditionally, trypsin's role in the mediation of disease by enzymatic degradation has been seen, at best, as a minor player amongst the host of these relatively non-specific enzymes. However, it now appears that tryptase is capable of eliciting discrete proasthmatic activity, both in animal tissues and human tissues in vitro.