New Compound Seen to Treat CF-linked Lung Ailments Independent of CFTR Mutation

Researchers at the Queen’s University Belfast developed a new compound that may change how lung ailments in cystic fibrosis (CF) are treated. The potential medicine was shown in an early study to improve airway hydration and increase mucus clearance, results that suggest a mechanism to potentially delay or prevent lung disease independently of the CFTR mutation.

The research article, “Inhibition of Protease-ENaC Signaling Improves Mucociliary Function in Cystic Fibrosis Airways,” was published in the American Journal of Respiratory and Critical Care Medicine.

In CF, airway clearance is compromised due to faulty airway surface liquid production, resulting in mucus accumulation and increased incidence of bacterial infections. This harmful cycle leads to chronic infections and airway inflammation, and a progressive decline in lung function.

Funded by The Cystic Fibrosis Trust and developed in collaboration with the Royal College of Surgeons in Ireland and the University of North Carolina, the study describes a new way of treating CF — namely, through the inhibition of the epithelial sodium channel (ENaC). The scientists developed a compound, called QUB-TL1, to inhibit protease/ENaC signaling in CF airways.

Results obtained in cell assays showed that QUB-TL1 reduced ENaC activity, which correlated with improved airway hydration status and mucus clearance. Moreover, the compound’s effects hint at a protection against Pseudomonas aeruginosa exotoxin A-induced cell death, the pathogen responsible for most bacterial lung infections in CF patients.

“This is an important finding which could provide a novel therapeutic opportunity relevant to all individuals with CF, as the targeting of ENaC is independent of their underlying CF mutation. This strategy could prevent the significant lung damage that results from chronic cycles of infection and inflammation, with potential impact on quality of life as well as life expectancy,” Dr. Lorraine Martin, one of the study’s lead authors, said in a press release.

The results are particularly important because this compound — a new protease inhibitor — works independently of the CFTR mutation present in a patient, in contrast to currently approved medicines that are mutation-dependent and, as such, effective in only small subsets of CF patients.