Last January, the FDA approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis. This year, scientists believe they’ve discovered exactly how the drug works, according to new research. New models proposed by the research team could target the root cause of cystic fibrosis and lead to improved treatments and outcomes, researchers believe.
The cystic fibrosis transmembrane conductance regulator (CFTR) is, according to researchers, like a pipe that allows ions to travel through at a very fast pace.
“In cystic fibrosis patients the channel is dysfunctional and activity is diminished. So what is the mechanism that controls the opening and closing of the channel?” asked Tzyh-Chang Hwang, PhD, PNAS corresponding author and professor of medical pharmacology and physiology at the University of Missouri School of Medicine. “That is the fundamental discovery of our recent papers summarized in Physiology.”
Investigators made an accidental discovery of a mutation in CFTR, the R532 mutation, allowing them to reveal a new “non-strict coupling” relationship between the consumption of ATP and the opening and closing of the CFTR. The team believes the new information uncovered about this mechanism controls the opening and closing of the CFTR and the passage of ions through it. The team thinks it could explain how and where Kalydeco (Vx-770) works.
“It’s taken years for scientists to solve this particular puzzle about the CFTR protein,” said Hwang. “Our recent study provides evidence that these ABC transporter proteins and CFTR, a chloride channel, are two peas in a pod. Mother nature employs the same structural framework with just a little bit of modification to do two totally different things. From a basic science perspective, it’s a big deal.”