Cystic fibrosis is a genetic disorder that affects around 700,000 people worldwide. Chronic lung infections that lead to lung damage are one hallmark of the disease. Treatments are limited, but new research may help change that. Scientists have determined that amphotericin, a common antifungal medication that is already on the market, could help CF patients that don’t respond to current therapeutics. The findings have been reported in Nature.
This illustration depicts a microscopic view of the lining of the lung surface of a person with cystic fibrosis (CF). In people with CF, a protein that releases bicarbonate, a key infection-fighting agent (represented by red spheres), is missing or defective (brown ribbon structure). The drug amphotericin (white structure) can form channels to release bicarbonate in lung tissue, restoring the antibiotic properties of the airway surface liquid, the thin layer of fluid covering the surface of the lungs that plays a key role in maintaining lung health. / Credit: Rebecca Schultz, Carle Illinois College of Medicine
"The really exciting news is that amphotericin is a medicine that's already approved and available on the market," said the study leader Martin D. Burke, M.D., Ph.D., a professor of chemistry at the University of Illinois in Champaign. "We think it's a good candidate."
Studies with human participants will be needed before the drug can be used in the clinic, but it could be a huge help to the ten percent of CF patients that don’t get any relief.
The disorder is caused by an error in the CFTR gene, which encodes for a protein that controls how chloride and bicarbonate move in and out of cells. A strict balance has to be maintained so that the cells will function properly. In CF patients, the protein is defective, and cannot move chloride ions to the surface of the cell, which means water isn’t attracted there, and sticky mucus forms. That mucus clogs the lungs and can trap stuff like bacteria, leading to a host of major complications including lung infections.
Many different errors in the CFTR gene can lead to the disease, which makes treating it challenging. Each of those mutations can cause a different problem with the protein, and not every treatment can correct every problem. Amphotericin is different, said Burke said; it could work no matter what the mutation is and even if the protein is gone.
Learn how CF affects the lungs from the video.
"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," Burke said. This so-called surrogate, in which the amphotericin acts as a kind of molecular prosthetic, restores function like a prosthetic device might.
In this work, lung tissue harvested from CF patients and animal models was exposed to amphotericin. That triggered many changes that are associated with better lung function, like improved viscosity, increased activity of antibacterials, and a restoration of proper pH levels.
Amphotericin can also be sent directly to the lungs of patients, which can reduce common side effects.
"The cystic fibrosis community is truly in need of new therapies to reduce the burden of this disease. We are interested to see how this potential treatment performs in clinical trials in the future," added James Kiley, Ph.D., director of the Division of Lung Diseases at the NHLBI.