Grant: Project Grant

Asthma is characterized by excessive constriction of the airways and inflammation in the lung. Ten percent of people in the world suffer from asthma and the prevalence increases by 50% every decade. Currently there is no cure for asthma; the available treatments only control the symptoms. Traditional drugs target two aspects of the disease; inflammation and airway constriction. Fatal asthma-attacks usually result from failed response of airway muscle to relaxant drugs. The fact that muscle relaxants and anti-inflammatory drugs do not cure asthma suggests that they are not targeting the root cause of asthma. Recent research in our laboratory has revealed a new drug target that may be related to the root cause of asthma. We have found that the stiffness of the relaxed airway muscle contributes to the overall stiffness of the airways, and is partially responsible for the reduced airway distensibility found in asthmatic patients. Interestingly the muscle stiffness does not respond to the traditional muscle relaxants, which is effective only on activated muscles. We found that a new class of drugs targeting the structural integrity of airway muscle cells is effective in reducing the cell stiffness, and in the presence of mechanical stretches similar to those experienced by the muscle in a breathing lung, the relaxant effect of the drugs on airway muscle is synergistically enhanced. In this application we propose to identify new drug targets that "soften" the airway muscle cells, making them more responsive to mechanical stretches imposed by breathing, which further softens the cells, leading to improved airway distensibility and dilation. The goal of our research is to provide a better alternative for treating asthma.