MICA: Determining the therapeutic potential of targeting the free fatty acid receptors FFA1 and FFA4 in human lung inflammatory disease

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Asthma is a chronic lung inflammatory disease that affects >300 million people worldwide, causing substantial morbidity and exacting a considerable cost to health services. Despite the effectiveness of current therapies still ~45% of asthmatics remain uncontrolled. Here we propose to investigate a novel way of treating asthma by raising drugs that activate receptor proteins that we have found are present in human lungs and that when activated can reduce inflammation and relax the airways allowing more air to get in and out of the lungs. These receptor proteins are normally activated by fatty acids such as omega-3 fatty acids that are found in our diet. It is somewhat surprising that receptor proteins that respond to dietary fatty acids are present in our lungs but we have found that this is indeed the case. We have also found that activation of these receptor proteins, called FFA1 and FFA4, can relieve many of the symptoms associated with inflammatory lung disease in mouse disease models that we have established. Here we will work together with our clinical colleagues who have access to normal human and diseased lung samples. Alongside additional studies that will take advantage of our expertise in mouse models of inflammatory lung disease we will assess if making drugs that activate FFA1 and FFA4 might potentially relieve symptoms and reduce inflammation in lung diseases such as asthma.