Asthma is a chronic disease of the lungs that can make breathing difficult. These episodes occur infrequently in mild cases or everyday in more severe cases. The difficulty in breathing is caused by inflammation in the airways of the lungs which leads to a thickening of the lining of these airways and spasticity of the muscles that line the bronchial tubes causing bronchospasm. Bronchospasm causes a sudden narrowing or tightening of the airways which is known as an acute asthma attack (also called an episode, flare-up, or exacerbation). Depending on the severity of the disease, asthma can be treated with oral and inhaled medications to relieve the bronchospasm and inflammation, and to mitigate the cascade of events that lead to the episode. These include bronchodilators, oral and inhaled steroids, leukotriene inhibitors, and anti-IgE therapies.

Complement activation in preclinical studies of Asthma

Preclinical studies using an anti-C5 complement blocking antibody significantly reduced the bronchial inflammation and airway constriction in a mouse model of asthma. The study, conducted by researchers at Alexion Pharmaceuticals, the Yale University School of Medicine and the Brigham and Women's Hospital, was published in the June 2005 issue of the Journal of Clinical Investigation. The study demonstrated that both C5a and C5b-9 contribute to the initiation of airway inflammation and in immediate and sustained airway hyperreactivity. It was shown that animals given an anti-C5 blocking antibody – either systemically or when inhaled through a nebulizer – showed substantial reductions in airway reactivity even in the face of 'airway challenges' with methacholine, a drug administered to confirm an asthma diagnosis. The findings also demonstrate that C5 blockade provides more comprehensive and significant reductions in both airway hyperreactivity and pulmonary inflammation than does blockade of a related target, C5a alone. The anti-C5 blocking antibody, unlike other existing asthma therapies – high-dose inhaled and oral corticosteroids – blocked a wide range of inflammatory mediators known to contribute to the severity and persistence of asthma, including white blood cells and inflammatory mediators released from eosinophils and neutrophils. This data suggests a direct role for complement-mediated inflammation in the pathogenesis of severe asthma. Alexion plans to evaluate the potential for clinical development of eculizumab in asthma.

For more information on Asthma please see the American Academy of Allergy, Asthma and Immunology at http://www.aaaai.org/ .