CIRM funded study may help explain why some people with cystic fibrosis are less prone to infection

Dr. Kelly A. Frazer, UC San Diego School of Medicine

Cystic fibrosis is a disorder that mostly affects the lungs. It is caused by a mutation in a gene called cystic fibrosis transmembrane conductance regulator (CFTR). As a result of this mutation, cells that produce mucus (a slimy substance like the one in your nose) secrete a thicker-than-normal mucus that can create blockages in the lungs and digestive system. In the lungs, this thicker mucus is a perfect breeding ground for bacteria, leading to more chronic lung infections in those with cystic fibrosis.

However, some people with cystic fibrosis don’t develop lung infections as early or as often as others with the disorder. Thanks to a CIRM funded study, Dr. Kelly Frazer and her team at the UC San Diego School of Medicine have discovered why this might happen.

In healthy people, the CFTR protein is embedded in the membrane of most cells, where it forms a channel for chlorine ions. In people with cystic fibrosis, an inherited mutation in the CFTR gene means their channels don’t work as well and cells produce more mucus. The RNF5 protein inhibits CFTR, so people with cystic fibrosis who have genetic variations that decrease RNF5 expression have CFTR channels that function a little better, and thus aren’t as prone to infections as people with high RNF5 expression.

Before we get into that, we need to dive a bit deeper into cystic fibrosis and what causes this thicker-than normal mucus. In healthy people, CFTR is embedded in the membrane of most cells, where it forms a channel that allows chloride – a component of salt – to travel through. This flow ensures that cells have the right balance of salt and water. In people with cystic fibrosis, the CFTR mutation means that the channel doesn’t work as well, the flow of water is blocked resulting in more thick and sticky mucus. There are medications that can help boost CFTR, but they are very expensive and don’t work for everyone.

Dr. Frazer and her team discovered that a gene, called RNF5, also prevents CFTR from functioning well. People with cystic fibrosis who have lower levels of RNF5 have channels that function better, with less mucus build up, compared to people with higher levels of RNF5. This could potentially explain why some with cystic fibrosis get more chronic lung infections compared to others with the condition.

In a press release by UC San Diego School of Medicine, Dr. Frazer talks about how RNF5 could play a role in treating patients.

“The cystic fibrosis field is trying to figure out what are the modifiers across the genome that increase or decrease the probability that an individual patient will respond to these expensive drugs. RNF5 may be one of these modifier genes.”

In the same press release, Dr. Matteo D’Antonio, a project scientist in Dr. Frazer’s lab, talks about how these findings could result in more personalized treatments for people with cystic fibrosis.

“This study uncovered a new aspect of cystic fibrosis — one that could lead to new drug design and development, and allow clinicians to better tailor treatments.”

The full study was published in eLife.

One thought on “CIRM funded study may help explain why some people with cystic fibrosis are less prone to infection

  1. Pingback: CIRM funded study may help explain why some people with cystic fibrosis are less prone to infection - Nebraska Coalition for Lifesaving Cures

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