Scripps Research Institute makes stride toward Cystic Fibrosis treatment

LA JOLLA (KUSI) – Just like some people talk too much and hang out with the wrong crowd, a mutant protein responsible for most cases of cystic fibrosis acts similarly, scientists at The Scripps Research Institute reported Monday.

The cystic fibrosis transmembrane conductance regulator protein is so busy communicating with the wrong neighboring cells that it can’t function normally and is prematurely degraded, the scientists concluded in a study published online in the journal Nature.

By removing the chatter, researchers partially restored the protein’s normal function, according to TSRI. The findings suggest that therapies could one day treat the root cause of cystic fibrosis, not just the symptoms.

"The proteins and the interactions we’ve identified really fuel the pipeline for new drug targets to treat cystic fibrosis,” said Casimir Bamberger, a TSRI research associate and co-author of the new study with staff scientist Sandra Pankow.

People with cystic fibrosis suffer from persistent infections and mucus build-up in the lungs. While there are treatments to deal with the symptoms — such as antibiotics for infections — there are no therapies that fully restore lung function.

When the researchers analyzed cell samples, they identified almost every protein CFTR interacted with — even tracking the secondary and tertiary protein interactions.

While it was thought that most mutant proteins just lack one or two crucial interactions, the CFTR mutant had acquired an entirely new network.

"Three hundred proteins changed their level of interaction, and an additional 200 proteins interacted with the mutated CFTR,” said Pankow. "It’s like the wrong people are talking to the mutated CFTR all the time.”

The researchers narrowed these mutant protein interactions to just eight key disruptive proteins, used a gene silencing approach to block the interaction of these proteins with the mutant CFTR, and found that the CFTR protein partially returned to normal function.

Pankow and Bamberger said the next step will be to look for drug candidates that could target the disruptive proteins.

The researchers also released their raw data publicly so other scientists can explore the clinical implications of CFTR interactions.

The study was supported by, among others, the National Institutes of Health and the Cystic Fibrosis Foundation.

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