An international team of scientists, led by the Universities of Leicester and Glasgow, has announced findings that could pave the way to a new treatment for asthma and chronic obstructive pulmonary disease (COPD).
The breakthrough findings, published today in Science Translational Medicine, identify a new class of drugs that reverse airway narrowing and inflammation in animal models of asthma and increase profoundly the relaxation of muscle cells from human lung samples.
The drugs used by the research team work in a way that is distinct from currently prescribed medicines for asthma and COPD. The findings describe a route to alternative treatments for patients suffering from severe forms of asthma and COPD, that are not controlled by current frontline treatments.
The new approach is centred on the activation of a protein that up until now has been known to respond to fats contained in our diet. The protein, called free fatty acid receptor 4 (FFA4), is found in the gut and pancreas, where it is activated by dietary fats including the fish oil omega 3. Once activated, FFA4 is known to help control levels of glucose in our blood.
Surprisingly, the research team found FFA4 is also present in human lung.
By designing a new class of drugs that activate FFA4 in the lung, the researchers found that the muscle that surrounds the airways relaxes, allowing more air to enter the lung. They also found that activators of FFA4 also reduced inflammation caused by exposure of mice to pollution, cigarette smoke, and allergens like house dust mites that cause asthma.
In this way they have established that activating FFA4 can reverse the key hallmarks of inflammatory lung disease, heralding the prospect of new drugs to treat it.
Professor Christopher Brightling, professor of respiratory medicine at the University of Leicester and a consultant in respiratory medicine at the University Hospitals of Leicester NHS Trust is a co-author of the paper. He said: “By the identification of this new mechanism we offer the hope for new effective medicines for those patients that are not responsive to our current treatments.”
Professor Graeme Milligan, Gardiner Chair of Biochemistry at the University of Glasgow, added: “We were delighted to see the effectiveness of this class of drugs in
relieving the symptoms caused not only by agents that result in asthma but also by pollutants and cigarette smoke.”
Professor Andrew Tobin, professor of molecular pharmacology at the University of Glasgow, also commented: “It was indeed a surprise to find that by targeting a protein that up to now has been thought of as being activated by fish oils in our diet we were able to relax airway muscle and prevent inflammation. We are optimistic that we can extend our findings and develop a new drug treatment of asthma and COPD.”
The paper, ‘Pathophysiological regulation of lung function by the free fatty acid receptor FFA4’ is published in Science Translational Medicine. The work was funded by the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC). It was supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre – a partnership between Leicester’s Hospitals, the University of Leicester and Loughborough University.