Researchers are evaluating drugs for their effectiveness in preventing, thinning, and breaking up the mucus in the airways. These drugs include CFTR modulators, ENaC inhibitors, CaCC activators, and mucolytics (mucus thinners).
By restoring function to the CFTR protein, CFTR modulators help restore the flow of chloride out of the cell and prevent mucus from becoming dehydrated, making it easier for people with CF to clear their lungs. Early clinical trial results have indicated the triple-combination modulators will likely be more effective than current modulators and could potentially treat a much larger population of people with CF.
Researchers also are working on drugs that are mutation-agnostic, which means they can help all people with CF regardless of their mutations. One such drug would prevent mucus from becoming dehydrated, inhibiting the hyperactive ENaC to enable more salt on the cell surface. The salt would then attract fluids, hydrating the mucus. Several ENaC inhibitors are under development in clinical trials.
In this video, Scott H. Donaldson, M.D., associate professor of medicine and director of the adult CF center at the University of North Carolina, talks about ENaC inhibitors and other approaches being explored to improve mucociliary clearance.