Antifungal drug improves key cystic fibrosis biomarkers in clinical study

CHICAGO, Dec. 18 (Xinhua) -- A drug widely used to treat fungal infections improved key biomarkers in lung tissue cultures as well as in the noses of patients with cystic fibrosis (CF), a clinical study by researchers at the University of Illinois (UI) and the University of Iowa found.

In previous work, the researchers demonstrated that amphotericin forms ion channels in cell membranes that perform similarly to the missing protein, acting as a prosthetic on the molecular scale to restore function on a cellular level.

In the new study, the researchers tested the drug in cultures of lung tissue from patients with cystic fibrosis. They confirmed that the drug increased ion secretion in the cultures. Then, in experiments designed to replicate the first clinical studies of the modulator drugs, they tested it in patients' noses.

The researchers assessed whether the drug increased ion flow in the nose cells by measuring a biomarker known as nasal potential difference. In the study, the nasal form of amphotericin B changed the nasal potential difference in a way that suggested that amphotericin was performing the job of the missing CFTR channels.

"Though amphotericin B is an imperfect surrogate for the CFTR protein, these results provide the first evidence that small-molecule ion channels can impact physiology in people with cystic fibrosis," said Rajeev Chorghade, the first author of the study. "These results encourage further clinical trials to determine whether inhaled amphotericin B can improve lung function and health-related quality of life in people with CF, especially those not on modulators."

In the next step, the researchers plan to perform a clinical study to determine whether amphotericin inhaled directly to the lungs would improve lung function and immune response in patients with cystic fibrosis.

The patients who participated in the clinical study were among the 10 percent of patients who cannot respond to modulator treatments, suggesting the antifungal drug, amphotericin B, could benefit all patients regardless of their mutation.

Cystic fibrosis is caused by a missing or defective ion channel in the lining of the lungs, called CFTR. This leaves patients vulnerable to lung infections. Treatments called modulators can help some but not all patients, based on which type of genetic mutation causes the symptoms.

The study, posted on UI's website on Thursday, has been published in the Journal of Cystic Fibrosis. Enditem