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Discovery could increase efficacy of promising cystic fibrosis drug
Date:3/21/2013

A little more than a year after the FDA approved Kalydeco (Vx-770), the first drug of its kind to treat the underlying cause of cystic fibrosis, University of Missouri researchers believe they have found exactly how this drug works and how to improve its effectiveness in the future. Described in the current issue of the Proceedings of the National Academy of Sciences, MU researchers have redefined a key regulatory process in the defective protein responsible for cystic fibrosis that could change the way scientists approach the lethal genetic disease.

"They know the drug works, but they don't know how it works or where it works," said Tzyh-Chang Hwang, PhD, PNAS corresponding author and professor of medical pharmacology and physiology at the MU School of Medicine. "Our paper provides a theory for how Vx-770 works, and based on our understanding of how the CFTR channel works, we have identified a novel strategy for future explorations to complement and enhance the performance of the existing drug."

Cystic fibrosis is the second most common life-shortening inherited disorder occurring in childhood in the United States, after sickle cell anemia. Approximately 30,000 Americans have cystic fibrosis, and there are an estimated 1,000 new cases diagnosed each year. Cystic fibrosis patients are born with a genetic defect that causes a malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel in the cell membrane that plays a critical role in maintaining water and salt balance across many body tissues, such as sweat glands, tissues that line the lungs, liver, pancreas and reproductive organs.

"The chloride channel is like a pipe that allows ions to travel through at a very fast pace," Hwang said. "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? That is the fundamental disco
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Contact: Michael Muin
muinm@health.missouri.edu
573-884-7541
University of Missouri School of Medicine
Source:Eurekalert  

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