Emerging treatments for asthma

Abstract

Despite the availability of a great number of medications, the asthma epidemic is continuing to increase. It is obvious that a high, unmet medical need remains and innovative therapeutic agents are urgently required. Existing therapies, such as β-agonists and corticosteroids, provide relief for sufferers of mild-to-moderate asthma, reversing the acute bronchoconstriction and decreasing the inflammation. However, these therapies provide little relief for chronic asthmatics. Asthma is a manifestation of an imbalance in cytokine and signalling pathways that mediate inflammatory and structural changes within the lung. New therapies need to be developed to target these changes. Emerging treatments for asthma include strategies to alter the cytokine/chemokine balance, to skew the cytokine profile away from a T helper (Th)2 response and towards a Th1 response. Strategies designed to do this include therapeutic antibodies or small molecule inhibitors targeted towards IL-13, IL-4 or their receptors, and the Th1 cytokine IL-12. Much interest has focused on the signalling pathways involved in asthma. Among these, the mitogen-activated protein kinase (MAPK) pathway members c-Jun N-terminal kinase (JNK) and p38 have gathered much interest, in addition to the transcription factors nuclear factor kappaB (NF-κB), activator protein-1 (AP-1) and signal transducer and activator of transcription (STAT)-6. This review aims to summarise the emerging treatments for chronic asthma, from early discovery, to late clinical stages, and discuss the therapeutic rationale behind these treatments. Much is still to be learned about the mechanisms involved in the development and treatment of chronic asthma; however, much promise lies in the future of these new therapeutics.

• asthma
• intracellular signalling
• small molecule inhibitors