Japanese researchers identify Interleukin-5 (IL-5) receptors as a target for preventing airway remodelling in asthma

DailyUpdates 2nd March - Today's breaking journal articles for the drug discovery community:  The number of Americans afflicted with asthma now exceeds 15 million and global revenues from asthma therapies has been reported by some to be in excess of $11 billion.  The anti-asthmatic market is well served by existing therapies, such as the b2-agonists and corticosteroids however the development of orally active therapeutics is awaited.  Drugs targeting interleukin-5 (IL-5) represent one key class of asthma therapeutics having been shown to be central to the inflammatory process; Japanese researchers now report that blocking IL-5 receptor activation also limits airway remodeling in asthma.

From 1980 to 1996, the number of Americans afflicted with asthma more than doubled to almost 15 million, with children under five years old experiencing the highest rate of increase. The steady rise in the prevalence of asthma constitutes an epidemic, which by all indications is continuing. Paralleling the dramatic growth in its incidence, asthma has driven one of the most rapidly growing global therapeutic markets now standing at in excess of $11.7 billion.  The anti-asthmatic market is well served by existing therapies, such as the b2-agonists and corticosteroids which can treat 95% of asthma patients.  Future advances are expected to come in the form of products which combine these approaches and also orally active therapeutics. 

IL-5 plays an essential role in orchestrating the eosinophilic inflammation of asthma. Humanized monoclonal antibodies to IL-5 have been developed and a single intravenous infusion of one of these antibodies (mepolizulab) markedly reduces blood eosinophils for several weeks and prevents eosinophil recruitment into the airways after allergen challenge in patients with mild asthma. Although it has been questioned whether blocking eosinophils can translate to therapeutic efficacy in an acute setting, blocking eosinophils by targeting IL-5 may improve more chronic aspects of asthma, such as airway remodeling.  For a full evaluation of emerging asthma therapeutics including a discussion of the potential benefit of targeting IL-5 click here.

In a recent paper, Tanaka and colleagues from Gifu Pharmaceutical University have reported that eosinophilia and fibrosis found in an experimental model of asthma are abolished in the absence of IL-5 receptor expression.  The authors conclude firstly that eosinophils are involved in allergen-induced subepithelial and peribronchial fibrosis probably by producing a fibrogenic factor, TGF-beta1; and secondly that blocking IL-5 signaling can prevent these changes.  This study thereby suggests that IL-5 receptor antagonists or monoclonal antibodies may be of benefit in preventing the more long-term and often irreversible problems associated with asthma.