In the United States, about 40,000 children and adults are living with Cystic Fibrosis (CF), a genetic disorder that often causes damage to the lungs and pancreas. Around 1,000 people worldwide are diagnosed with the disorder every year, usually by age 2.
Decades ago, CF was a death sentence in childhood, but ongoing research has led to advancements in treatment that are helping CF patients live comparatively long lives, well into their 50s. Despite that, treatment still has a long way to go, and new research out of Yale University this month points toward a promising new avenue.
CF disrupts a protein in the body that regulates chloride in cells. Without it, mucus in the body (usually the lungs) becomes thick and sticky. Eventually, that traps germs and bacteria and leads to chronic infections and lung damage. Treatments for CF include therapeutic vests, inhaled medications, antibiotics, protein modulators, and, in extreme cases, lung transplants.
In a study published in the December issue of Cell Reports, Yale researchers explain that while current therapies have drastically increased the life expectancy of CF patients “long-term studies of patients suggest that these therapies are not sufficient to control lung hyperinflammation over time.”
Researchers looked at lung tissue from patients with advanced CF and found that they had high levels of monocytes. They then turned to mice with chronic lung inflammation, approximating damage done in CF patients. In studying how the monocytes acted, they found that they release a chemical attractant that draws something called neutrophils into the tissue which causes lung damage.
“Pro-inflammatory monocytes are part of the normal immune response, but once they arrive and do their job, they should be instructed to leave and be silent,” Emanuela Bruscia senior author of the study and associate professor of pediatrics at Yale School of Medicine told Yale News. “But in cystic fibrosis, they arrive, they are super inflammatory, and then they are in an environment in which they can’t leave and be silent, so instead, they keep producing these pro-inflammatory mediators.”
To counter the issue, the researchers used a CCR2 inhibitor to bring the number of monocytes down to healthier levels. They found that, by using the inhibitors, they were able to reduce the amount of tissue damage.
As a result, the researchers concluded that a CCR2 inhibitor “prevents lung tissue damage and, thus, may be a potential therapeutic target to preserve lung function in patients with CF.” Further research is needed to determine exactly how effective the inhibitors could be and whether different types work better for CF patients, but for now it presents an exciting new avenue of research.
