An international team of scientists, led by the Universities of Leicester and Glasgow, have announced findings that could pave the way to a new treatment for asthma and chronic obstructive pulmonary disease (COPD) and reverse the key hallmarks of inflammatory lung disease.
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 present in human lungs.
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 reduced inflammation caused by exposure of mice to pollution, cigarette smoke, and allergens like house dust mites that cause asthma.
According to Asthma UK, 5.4 million people in the UK are currently receiving treatment for asthma: 1.1 million children (1 in 11) and 4.3 million adults (1 in 12).
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 who are not responsive to our current treatments.”
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.
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.”
Reference: Prihandoko, et al. (2020). Pathophysiological regulation of lung function by the free fatty acid receptor FFA4. Science Translational Medicine. DOI: 10.1126/scitranslmed.aaw9009
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