Emerging drugs for asthma.
BACKGROUND
Current therapies for asthma are aimed at controlling disease symptoms and for the majority of asthmatics inhaled corticosteroid anti-inflammatory therapy is effective. However, this approach requires life-time therapy while a subset of patients remains symptomatic despite optimal treatment creating a clear unmet medical need.


OBJECTIVE
It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches may identify new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach may provide disease-modifying treatments.


RESULTS
Significant areas of drug development include humanised monoclonal antibodies (mAb) for asthma therapy including those against IgE, IL-4 and IL-5. Asthma-relevant cytokines or chemokines have been targeted in a number of other ways. These include the use of humanised receptor blocking mAb or the removal of cytokines or chemokines via their binding to soluble receptor constructs. Small-molecule receptor antagonists also target receptors or the cellular signal transduction pathways that are activated following cytokine or chemokine receptor ligation. Another approach is to target asthma relevant mediators or the pathways controlling pro-inflammatory leukocyte accumulation within the asthmatic lung.


CONCLUSIONS
This review will discuss the current status, therapeutic potential and potential problems of these novel drug developments in asthma therapy. Current therapies for asthma are aimed at controlling disease symptoms, and for the majority of asthmatics inhaled corticosteroid anti-inflammatory therapy is effective. However, this approach requires lifetime therapy; and a subset of patients remains symptomatic despite optimal treatment, creating a clear unmet medical need. It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches may identify new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach may provide disease-modifying treatments. Significant areas of drug development include humanised mAb for asthma therapy, including those against IgE, IL-4 and IL-5. Asthma-relevant cytokines or chemokines have been targeted in a number of other ways. These include the use of humanised receptor blocking mAb or the removal of cytokines or chemokines via their binding to soluble receptor constructs. Small-molecule receptor antagonists also target receptors or the cellular signal transduction pathways that are activated following cytokine or chemokine receptor ligation. Another approach is to target asthma-relevant mediators, or the pathways controlling pro-inflammatory leukocyte accumulation within the asthmatic lung. This review will discuss the current status, therapeutic potential and potential problems of these novel drug developments in asthma therapy.
Walsh
Garry M
GM
Division of Applied Medicine Institute of Medical Sciences, University of Aberdeen Foresterhill, Aberdeen AB25 2ZD, UK.
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015507:Drugs, Investigational; D018836:Inflammation Mediators