The airway is the focus of two highly prevalent diseases, COPD and asthma. There is a pressing need to develop new treatments for chronic obstructive bronchitis and emphysema, together known as chronic obstructive pulmonary disease (COPD), as no currently available drug therapy reduces its relentless progression. World-wide, 600 million people suffer from COPD, with some three million dying from the disease each year representing a global market of US$2.8 billion US. There is a particular need to develop drugs that control the underlying inflammatory and destructive processes that cause COPD. 

Asthma is also very common, affecting 155 million people worldwide. In the United States alone there has been a recent 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, like COPD, is an inflammatory disorder of the airways and the development of anti-inflammatories represents an obvious way forward for their treatment, although the identification of suitable targets represents a considerable challenge. Asthma is mediated by Th2 lymphocytes, which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Targeting these cytokines, especially IL-13 has emerged as an approach to the treatment of asthma. The ADAM family of membrane-anchored proteins has a unique domain structure, with each containing a disintegrin and metalloprotease (ADAM) domain. This family is implicated in cell-cell interactions, cell fusion, and cell signaling. Of particular relevance to inflammatory disease, the ADAM proteins are involved in the shedding of cell-surface proteins such as cytokines and cytokine receptors and may therefore be implicated in the pathophysiology of diseases such as asthma. At the beginning of 2002, Japanese researchers reported the cloning of a novel member of the ADAM family, ADAM33, and further research has shown that this protein is most highly expressed in the adult brain, heart, kidney, lung and testis. This expression profile implicates ADAM33 in airway inflammation. Most recently a collaboration of researchers at Genome Therapeutics, the University of Southampton and Schering-Plough Corporation have linked ADAM33 to the pathophysiology of asthma. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In their study these researchers identify ADAM33 as a putative asthma susceptibility gene. Thus the role of ADAM proteins in the regulation of inflammation, the expression profile of ADAM33 and its possible etiological/hereditary role in asthma all point to this particular ADAM protein as a target for airway disease.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk