Amphotericin to Fight Cystic Fibrosis? Researchers Hope Human Trials Prove Early Results

The fungal drug amphotericin, which was discovered in 1953, could possibly help patients with cystic fibrosis (CF) fight chronic bacterial lung infections if results from an early study are validated in humans, researchers said Wednesday.

According to researchers at the University of Illinois and the University of Iowa, amphotericin acts as a protein channel that is missing in the lungs of those with CF, “operating as a prosthesis on the molecular scale,” according to a statement from the universities. Amphotericin restored infection-fighting properties in lung tissue donated by human patients as well as in pigs with CF, which is caused by a defect in the gene called CFTR (cystic fibrosis transmembrane conductance regulator).

There are 3 CFTR inhibitors approved to treat the underlying cause of CF, but they only work in people who have specific types of genetic mutations, the most common cause of CF. The researchers said amphotericin has the potential to become the first treatment to address all types of CF, regardless of which genetic mutation is involved, and even when the protein is missing.

The findings from the study appeared in the journal Nature.

The CFTR gene normally makes a protein that controls or channels the movement in and out of cells of such materials as salt, bicarbonate, and water. In CF, the defective gene makes a protein that is itself defective, causing the accumulation of acidic and sticky mucus that not only clogs the lungs and makes it hard to breathe, but also makes the lungs vulnerable to bacterial infection.

“Instead of trying to correct the protein or do gene therapy—the latter of which is not yet effective in the lung—we use a small molecule surrogate that can perform the channel function of the missing or defective protein,” said Martin D. Burke, MD, PhD, lead investigator and professor of chemistry at the University of Illinois in Champaign.

Amphotericin restored pH levels, improved viscosity, and increased antibacterial activity. He noted that the drug is already on the market and can be delivered directly to the lungs to avoid common adverse events.

About 10% of patients with CF do not respond to any treatment. More than 30,000 people in the United States and 70,000 worldwide have the disease, which is incurable.

The research was supported in part by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Reference

Muraglia KA, Chorghade RS, Kim BR, et al. Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia [published online March 13, 2019]. Nature.

doi.org: 10.1038/s41586-019-1018-5.