In a world where the prevalence of antibiotic resistance is growing and the development of new classes of antibiotics is slowing, how can we continue to effectively treat diseases like cystic fibrosis?

In a new study published in the journal Nature Communications, researchers at the University of Cambridge and at Yale attempted to address this question, identifying a novel technique for personalizing treatment for cystic fibrosis.

“There is a growing interest in personalized medicine because fewer and fewer drugs are available and antibiotic resistance is growing,” explained Maurizio Chioccioli, first author on the paper and postdoctoral associate at the Yale School of Medicine. “This work can be applied to screen the best possible therapy for a patient, but can also be used for drug screening, optimizing drug concentration and understanding the function of specific genes.”

Cystic fibrosis is a genetic disease caused by a mutation in the CFTR gene, which maintains the balance of salt and water on the surface of the lung. In patients with this mutation, the body produces a thick and sticky mucus instead of mucus that is thin and slippery. Though normal mucus functions as a lubricant, patients with cystic fibrosis produce mucus that plugs up passageways and tubes, according to the Mayo Clinic.

As a result, motile cilia — hairlike structures found on cells throughout the respiratory tract — are unable to push the thick mucus out of the respiratory tract, preventing the expulsion of invading pathogens and dirt that may enter the body. Therefore, without the ability to expel the mucus, patients with cystic fibrosis are prone to chronic infections resulting from the trapped pathogens.

In the study, the research team cultivated cells with motile cilia in vitro from several patients with different cystic fibrosis mutations. They used high-speed video microscopy and a video analysis algorithm to observe the cells with the different mutations and compared these cells to normal respiratory tract cells. They then treated the cells with six different drugs and observed the responses of the motile cilia present on the cells.

This novel technique allowed the researchers to quantify the efficacy of antibiotics on restoring normal cilia movement in different patients.

“In this case, we were using drugs that are approved and screening drugs, and showing that the same drugs have different levels of success in different patients,” Chioccioli said.

Chioccioli explained that even cystic fibrosis patients with similar genetic mutations have different responses to different treatments. He added that he hopes that this new method of studying how drugs restore the beating motion of cilia will help both researchers and physicians respond to cases of cystic fibrosis in an efficient and effective manner.

According to the Cystic Fibrosis Foundation, more than 30,000 individuals in the U.S. have cystic fibrosis, and approximately 1,000 new cases of cystic fibrosis are diagnosed in the U.S. each year.

Madison Mahoney | madison.mahoney@yale.edu

MADISON MAHONEY