UCLA researchers publish study on the effects of cystic fibrosis on lung cells

UCLA researchers published a new study in May on how a life-threatening lung disorder affects patients’ cells.

Cystic fibrosis is a genetically inherited disease that causes a buildup of mucus in the lungs and makes it harder to breathe over time, according to the Cystic Fibrosis Foundation. It affects about 30,000 people in the U.S. and around 70,000 globally, said Brigitte Gomperts, a professor of pediatric-hematology and one of the study’s co-authors.

The researchers found there were several key differences between the lung cells of patients with and without CF.

Patients with severe CF do not have a functional protein that normally assists in clearing built-up mucus from the lungs, Gomperts said.

Mucus is the body’s greatest defense mechanism, Gomperts said, trapping microscopic invaders such as bacteria and viruses. However, individuals with CF are unable to clear old mucus, allowing germs to accumulate and cause chronic infections.

Current treatments for CF include medications and mechanical ventilators that are used to thin down and remove mucus from airways. However, these treatments do not work in patients that have severe CF, Gomperts said.

“Currently, the … drug therapies are only effective in between 85 and up to 90% of individuals with fibrosis,” said Scott Randell, a cell biology and physiology professor at the University of North Carolina at Chapel Hill, a co-author on the study.

CF patients may be able to reach adulthood without extensive medical intervention, though they typically require lung transplants in order to live to middle age, said Justin Langerman, a biological chemistry researcher at UCLA and a primary author of the study.

Gene therapy could become a common treatment in the medical field that could potentially cure patients with genetic disorders like CF, Randell said.

The study could inform future gene therapy procedures, as gene therapy could treat CF by inserting a correct copy of the affected gene into a patient’s stem cells, Randell said. The treated stem cells would then mature and become healthy lung cells, potentially providing a decisive cure to the disease compared to current treatments, which provide temporary relief from symptoms, Gomperts said.

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The Cystic Fibrosis Foundation recruited Gomperts, along with other experts across the U.S., to understand key differences between CF patients and healthy individuals to complement research on potential gene therapy treatments, Gomperts said.

The research group created a detailed map of the various types of cells in the lungs to realize each type’s unique function, Gomperts said. These cells include those that produce mucus, cells that move mucus out of the airways and a store of stem cells – special immature cells that can transform into the other two types – Gomperts added.

The CF patients had lower amounts of immature cells compared to healthy patients, which made it harder for them to regenerate new lung cells and repair damaged tissues, Gomperts said.

The research would not have been possible without the use of modern genetic sequencing technology to map out the cells of the airway, Gomperts said.

Researchers had been working on potential cures for CF after discovering the genetic basis for the disease in 1989, Randell said. There had not yet been a study analyzing the lung cells of CF patients in as much detail, he added.

Randell said the possibility of a permanent cure for CF using gene therapy would allow young children to not depend on medications for the rest of their lives. “For those kinds of therapies, we really need to understand the cell biology,” Randell said. “That’s why this study is important.”