Investigators focused on cystic fibrosis know that a mutation--ΔF508, or delta-508--in the gene that encodes a protein called the cystic fibrosis transmembrane conductance regulator interferes with the proper folding of CFTR needed for it to be processed in cells, making it a leading cause of the disease.
They also know from earlier work that at low temperatures, mutant CFTR can partially regain its normal function.
So a group at The Scripps Research Institute in La Jolla took the next logical step. They set out to find a new therapeutic approach that would mimic the impact of low temperatures on delta-508.
In their work, they found that mutant CFTR becomes almost hyperactive after developing what they termed a disease-specific interaction network.
"Three hundred proteins changed their level of interaction, and an additional 200 proteins interacted with the mutated CFTR," said Scripps researcher Sandra Pankow. "It's like the wrong people are talking to the mutated CFTR all the time."
So they shut down much of the chatter.
Using gene silencing tech, they were able to eliminate most of the protein interactions, and in the process regained part of the normal functioning of mutant CFTR. And they believe the project could help point the way to new therapies that address the disease, rather than simply focusing on the symptoms.
The work--funded by the NIH--is being published in the journal Nature.
- here's the release
- read the journal abstract