Scientists have identified a compound that triggered long-lasting airway relaxation and prevented hyperreactivity in mouse models of asthma, potentially paving the way to a new therapeutic target for multiple breathing disorders. Patients with asthma, emphysema, and other obstructive lung diseases often need combination therapies to relax constricted smooth muscles in their airways. What's more, current treatments only provide partial relief because multiple members belonging to a family of proteins called G-protein coupled receptors (GPCRs) contribute to chronic airway hypersensitivity. It is known that several airway GPCRs partner with one specific G-protein called Gq, and here, Michaela Matthey et al. demonstrated that inhibiting Gq provided prolonged protection against airway constriction. The scientists showed that a Gq-inhibitor called FR relaxed constricted mouse, pig, and human airways ex vivo. Importantly, the compound could also be delivered as an inhaled aerosol, and the effects of a single dose persisted for at least 24 hours in mouse models without impacting blood pressure or heart rate in the animals. In two different mouse models of asthma, FR hindered airway hyper-responsiveness in response to allergens without causing cardiovascular side effects. FR inhalation did not alter inflammation in mouse models of asthma, but the compound did block some aspects of airway remodeling that occurs in the disease. The authors say more studies with larger animal models could further confirm FR as a promising new airway relaxation agent for obstructive lung disease. They also note that future work will need to investigate longer-term FR effects on other organs, and during chronic application.
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Journal
Science Translational Medicine