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Researchers at the University of Iowa and the University of Missouri have developed a better animal model of cystic fibrosis. Newborn pigs that have been bred with a genetic mutation for the disease are the first animals to exhibit clinical symptoms similar to those in humans with the condition. The results point to a more effective way of studying cystic fibrosis and finding drugs to treat it.

Cystic fibrosis is one of the most common life-shortening hereditary diseases. It affects 30,000 people in the United States and 70,000 worldwide. For years, scientists have tried to track the disease in mice engineered with the genetic mutation for cystic fibrosis, but the mice have not developed the trademark symptoms, including chronic lung disease. The pigs, whose organs are a closer match with humans, developed lung disease several months after birth. The researchers have published the results in the current issue of Science Translational Medicine.

Part of the motivation for the research is that, while the genetic root cystic fibrosis has long been known, it’s still unclear how this leads to lung disease.

The team found that newborn pigs with the disease had elevated levels of bacteria in their lungs. This finding may help resolve a long-standing debate –whether people with the disease are born with a hypersensitive inflammatory response that leads to lung disease, or whether inflammation occurs only when bacteria are present.

“One question looming in the field is this chicken or egg concept of whether infection comes first, or whether inflammation precedes,” says David Stoltz, assistant professor of pulmonary, critical care and occupational medicine at the University of Iowa, who was involved in the project. “It’s important to answer that question because if you now know the sequence of events of lung disease in cystic fibrosis, that could dictate how you treat it.”

Currently, physicians may choose to aggressively treat both infection and inflammation to slow the progression of lung disease. However, if researchers identify which of the two comes first in the disease, doctors could focus therapies to treat it much earlier, potentially extending lung function.

In order to identify the early effects of cystic fibrosis, Stoltz and his colleagues observed the genetically engineered pigs from birth. Within months, the pigs developed signs of lung disease, including airway inflammation, mucous accumulation, and bacterial infection.

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Credit: David K. Meyerholz

Tagged: Biomedicine

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