Affecting approximately 30,00 people in the US, cystic fibrosis (CF) is a genetic condition that, in 75% of cases, is diagnosed before the age of two. Inherited in an autosomal recessive manner, CF results from a mutation in the cystic fibrosis transmembrane conductance regulator (CTFR) gene.
Under normal conditions, this gene encodes a protein that controls the movement of molecules such as salt, bicarbonate and water across cell membranes in the lungs. In CF, the genetic mutation produces a faulty protein that results in a build-up of an acidic and sticky mucus; clogging the lungs, making breathing extremely difficult, and increasing susceptibility to infection.
Whilst lung infections can be treated with antibiotics, sadly, no cure is currently available for CF. Receiving a diagnosis can therefore be an extremely emotional and daunting time for families. According to Cystic Fibrosis Foundation National Patient Registry, the median age of survival for a person with CF is currently 33.4 years, however this varies depending on the severity of each individual’s case. Severity is defined by class, and a patient may be class I – V, depending on the type of mutated protein they produce.
The British Lung Foundation statistics suggest that one in 25 people carry the faulty CF gene. Whilst Cascade screening can identify whether an individual is a carrier (a service typically offered to relatives of those that have received a diagnosis), the lack of efficacious treatment options available is a major issue for CF sufferers.
A novel treatment approach
In a study published today in Nature, researchers from the University of Illinois, supported by the by the National Heart, Lung, and Blood Institute (NHLBI), suggest that a widely-used anti-fungal drug, amphotericin, may offer hope for CF patients and families.
The scientists applied amphotericin to human lung tissue from patients with CF and also pig cell CF models. They found that amphotericin induced a variety of changes associated with improved lung function in both models, including improved viscosity and increased antibacterial activity. The treatment may therefore help CF patients fight off chronic bacterial lung infections.
Speaking of the research, Martin D. Burke, leader of the study and professor of chemistry at the University of Illinois, said “the really exciting news is that amphotericin is a medicine that's already approved and available on the market”.
The study has sparked excitement in the field as the medication has the potential to be efficacious regardless of which mutation a CF patient possesses, or even if they possess no CTFR protein at all.
"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 [amphotericin] that can perform the channel function of the missing or defective protein," Burke said.
Validating the findings in humans
The next step is to explore whether human studies validate the findings. Amphotericin can be delivered directly to the lungs to avoid common side effects; however further research is required before the drug is safe to introduce directly into humans.
The scientists are hopeful that this treatment, already available on the market for other medical conditions, could provide a new avenue of hope for symptomatic relief for CF patients.
"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," said James Kiley, director of the Division of Lung Diseases at the NHLBI.
Reference: Muraglia et al. 2019. Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia. Nature. DOI: https://doi.org/10.1038/s41586-019-1018-5.