There is a pressing need to develop new treatments for the chronic obstructive pulmonary diseases (COPD), chronic obstructive bronchitis and emphysema. World-wide, 600 million people suffer from COPD, with some three million dying from the disease each year. This serious healthcare problem is paralleled by a global market of US$2.8 billion. There is a particular need to develop drugs that control the underlying inflammatory and destructive processes that cause COPD as no currently available drug therapy reduces the relentless progression of COPD. In contrast to the enormous advances made in asthma management little significant progress has been made in COPD therapeutics.

Although COPD is commonly treated with drugs developed for asthma, this is often inappropriate as the inflammatory process in COPD differs markedly from that in asthma. This phenomenon is well demonstrated by clinical responses to corticosteroids. This class of therapy has long been used in patients with severe asthma, however, four large 3 year controlled trials of inhaled corticosteroids have demonstrated no reduction in COPD progression. Despite these studies systemic corticosteroids are routinely used for the treatment of acute exacerbations of COPD and inhaled corticosteroids are increasingly prescribed for the long-term treatment of patients.

In our recent analysis of COPD, produced in collaboration with field-leader Peter Barnes, we highlight the clinical needs and pharmaceutical development surrounding COPD and review emerging pharmaceutical targets. One area of interest relates to the identification and reversal of corticosteroid resistance that has been proposed to occur in COPD. In addition we analyze the therapeutic potential of airway matrix metalloproteinase inhibitors. In a recent study, University of Colorado researchers have linked these two fields.

This group has found that rats treated with methylprednisolone were characterized by an increase in airway matrix metalloproteinase-9 activity and emphysema-like changes in airway structure. Rats treated concomitantly with methylprednisolone and a broad-spectrum matrix metalloproteinase inhibitor did not however develop emphysema. These data therefore suggest that corticosteroid treatment could be self-limiting further underlining the need for a better understanding of corticosteroid action in COPD, and more generally improved and novel approaches to the disease.

Entry date January, 2003

Adapted from Choe et al, Am J Respir Crit Care Med 2003 Jan 9; [epub ahead of print] - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.