Small molecule inhibitors and primary airway fibroblast activation in severe asthma

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Asthma is a common and disabling problem for many, particularly those with severe persistent disease that prevents them living a normal life. In these individuals the disease leads to a progressive decline in lung function despite standard asthma therapies and the airways are left permanently impaired. Our research has shown that this can be linked to scarring within the airway wall. Such scarring is due to the deposition of collagen from activated cells called fibroblasts. This research has also demonstrated that fibroblasts, grown in the laboratory from small samples of the airway lining tissue (biopsies), from patient volunteers with severe asthma generate more collagen than do fibroblasts grown from biopsies obtained from the airways of either healthy non-asthmatic volunteers or volunteers with mild asthma. Additional studies have suggested that specific intracellular signalling pathways may be involved in this altered response. This industrial collaboration with UCB Celltech provides access to small molecule pathway inhibitors that allow the undertanding of the relevance of these pathways to the altered synthetic function of these fibroblasts. Through this better understanding it will be possible to target specific disease processes that hopefully will lead to novel therapies that in the future will prevent the progressive decline in lung function in asthma