Attacking cystic fibrosis at its roots

EAST LANSING, Mich., Nov. 19, 2019 – Breakthroughs in cystic fibrosis are finally happening. While the latest CF headlines tout a new genetic treatment that targets its underlying cause, a major challenge still remains: How will we get rid of the chronic lung infections that plague CF patients? A Michigan State University scientist is trying to understand how these complex infections cause such a terrible disease.

Through a $2.7 million National Institutes of Health grant, MSU and Spectrum Health are examining the ubiquitous anaerobic bacteria found in all CF patients, which are often dismissed as a non-factor by scientists.

“While the newly approved Trikafta medication isn’t a cure, it certainly has demonstrated positive health benefits for those suffering from the disease; even patients on Trikafta will still battle chronic lung infections,” said Robert Quinn, MSU assistant professor of biochemistry and molecular biology, who’s leading the grant. “We must use a dual approach of treating the underlying cause and targeting lung infections if we want to ever eliminate the disease.”

Cystic fibrosis is a progressive, life-threatening disease that causes thick mucus to build up primarily in the lungs as well as other parts of the body. Doctors treat the chronic lung infection with increasingly aggressive antibiotics. While many scientists don’t understand the effects of antibiotic treatment against CF infections, this is the traditional approach to most, if not all, patients.

“The microbiome research led by Dr. Quinn is extremely important. People with cystic fibrosis frequently develop lung infections,” said Spectrum Health pulmonologist Marc McClelland, MD. “This research should help us to gain a better understanding of these infections and allow us to more effectively treat patients. In doing so, the ultimate goal is to improve their lung function and overall health.”

Quinn’s team is focusing on the bacteria that thrive in the lungs as thickening mucus cuts off their oxygen supply. Counterintuitive as it may seem in the lung, these anaerobic bacteria live without oxygen and are frequently present in CF-infected lungs, but little is known about their role as pathogens or contributors to CF.

Quinn’s team is focusing on pulmonary exacerbations, the flare ups that prompt hospital stays involving an increase in symptom severity, loss of lung capacity and an aggressive antibiotic treatment. During these flare ups, a turnover in the bacteria populations takes place; the anaerobic bacteria shift gears to thrive and dominate.

“Many doctors treating patients aren’t aware of these anaerobes,” Quinn said. “There’s still plenty of guesswork in treating CF. Antibiotics are prescribed, flare ups temporarily subside and the patient gets to leave the hospital; but sometimes they don’t improve and doctors don’t understand why.

“We believe that physicians have not been treating the principal cause of the flare ups – the anaerobes,” Quinn said.

By partnering with Spectrum Health, the scientists will be able to collect many samples from patients suffering from cystic fibrosis and study the microbial dynamics that drive the disease. They’ll also use a new model developed at MSU that mimics a CF-infected lung so they can test their hypothesis in a more realistic environment.

In addition, the team will utilize cutting-edge multi-omics methods, including microbiome sequencing, metabolomics and novel bioinformatics data analysis platforms, essentially taking a big-data approach to reveal clues toward a cure, Quinn said.

“Our scientific rationale is that a better understanding of what causes microbial changes during these flare ups will lead to more efficacious and targeted therapy against pathogens,” he said.

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Michigan State University has been working to advance the common good in uncommon ways for 160 years. One of the top research universities in the world, MSU focuses its vast resources on creating solutions to some of the world’s most pressing challenges, while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges.

Contact: Layne Cameron, University Communications: (517) 353-8819, (765) 748-4827, camer102@msu.edu; Robert Quinn, Biochemistry and Molecular Biology: (517) 353-1426, quinnrob@msu.edu

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