A new molecule that blocked ion channels in lab cells could significantly reduce the cycles of airway inflammation and infection that eventually result in fatal destruction of the lungs in people with cystic fibrosis. The researchers who discovered this suggest treatments based on the new molecule – a protease inhibitor – could potentially prolong the lives of people with the life-limiting disorder.

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The researchers believe treatments based on the new molecule could prevent the significant lung damage seen in people with cystic fibrosis and potentially increase their quality of life, as well as life expectancy.

Writing in the American Journal of Respiratory and Critical Care Medicine, the team – including researchers from Queen’s University Belfast in the United Kingdom – explains how the new molecule prevents activation of the epithelial sodium channel ENaC.

Experiments on cell cultures in the lab showed that the molecule has the potential to improve airway hydration and significantly improve mucus clearance.

Senior and corresponding author Dr. Lorraine Martin, from Queen’s University School of Pharmacy, says:

“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.”

Cystic fibrosis (CF) is a genetic disorder that damages the internal organs, especially the lungs and digestive system. According to the World Health Organization (WHO), the disease affects around 100,000 people worldwide.

As treatments have advanced, the number of adults with CF has steadily increased. Only 30 years ago, a person with CF was not expected to reach adulthood. Today, around half of patients with CF live more than 30 years, and some even live into their 50s and 60s.

A person must inherit two defective copies of a faulty gene called CFTR – one from each biological parent – to have CF. Each time two carriers of the gene conceive, there is a 25 percent chance that the child will have the disorder.

The faulty gene disrupts channels that allow ions to move in and out of cells, resulting in the mucus coating on tissue surfaces – for example, the lining of airways and the digestive tract – to become dehydrated, thick, sticky, and difficult to clear away.

The sticky mucus traps bacteria, giving rise to chronic infections, inflammation, scarring in the lungs, and difficulty digesting food.

For the study, the researchers tested the effect of the molecule on primary airway epithelial cells cultured in the lab.

They found that the molecule inhibits a number of channel-activating enzymes, “the activities of which are observed at excessive levels” on the surface of CF airway epithelial cells.

Inhibition of the enzymes reduced sodium channel activity, which is known to correlate with improved airway hydration and mucus clearance.

The authors conclude that the molecule could provide “a mechanism to delay or prevent the development of CF lung disease in a manner independent of CFTR mutation.”

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.”

Dr. Lorraine Martin

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