Asthma is now thought to affect 155 million people worldwide. In the United States alone there has been a two-fold increase in the number of cases of asthma driving pharmaceutical market values up to as high as $8 billion worldwide. Despite a large number of drugs available to clinicians, up to 15% of patients suffer from uncontrollable disease symptoms, increasing the demand for novel therapies that possess new modes of action. Asthma is an inflammatory disorder of the airways involving multiple mediators and cell types and although the development of anti-inflammatories represents an obvious way forward for the treatment of asthma, the identification of suitable targets represents a considerable challenge. Furthermore, there is also a considerable risk that targeting the immune system could compromise host defense systems. Even if the immune system can be satisfactorily controlled, a body of data suggests that problems associated with defective airway remodeling may remain, precluding optimal treatment of asthma. An alternate approach has been the development of mucoactive agents. This class of drug is intended to increase the ability to expectorate sputum (for example by increasing mucos fluidity) or to decrease mucus hypersecretion. Ca2+-activated Cl- channel 1 (CaCC1) has been identified as a protein that is expressed in intestinal epithelia and that plays an important role in fluid and electrolyte transport. Recently, its mouse counterpart, gob-5, was identified as a key molecule in the induction of murine asthma through mucus overproduction. To elucidate the relationship of CaCC1 to human asthma, Japanese researchers examined CaCC1 expression in bronchial tissues from patients with asthma and normal control subjects. The expression of CaCC1 was significantly upregulated in patients with bronchial asthma compared with control subjects. In situ hybridization and immunohistochemical analysis demonstrated that CaCC1 is located in the bronchial epithelium, especially in mucus-producing goblet cells. In vitro transfection of a CaCC1 expression vector into the human mucoepidermoid cell line, NCI-H292, increased mucus production and induced the MUC5AC gene. These results suggest that CaCC1 plays a direct role in mucus production and differentiation in goblet cells and may contribute to the pathogenesis of asthma through its mucus-inducing activity. This group has therefore defined a new target for the development of asthma drugs and has also developed a primary assay able to screen for mucoactive agents. Collaboration could speed the development of new therapeutic candidates. In a recent dossier (click here for access) we overview future options for the treatment of the serious and common conditions of emphysema and chronic bronchitis (COPD). Current feeling is that first line treatment of COPD should reduce inflammation or produce airway remodeling. However, since COPD is associated with mucos hypersecretion, mucolytic drugs have been developed as long-term therapeutic options for this disease as well as asthma. It would therefore be of interest to determine CaCC1 expression in bronchial tissues from patients with COPD

Link to journal abstract:

Adapted from Hoshino et al, Am J Respir Crit Care Med 2002 Apr 15;165(8):1132-6

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