A University of Missouri researcher believes his latest study looking at the two most common genetic mutations among the approximately 1,500 mutations found in patients with cystic fibrosis could lead to a cure for the disease. The paper, published in the Journal of Biological Chemistry, has been recognized as the “paper of the week” for the journal, meaning the work is considered to be in the top 1% of papers reviewed annually in terms of significance and overall importance.
Tzyh-Chang Hwang, a professor in the School of Medicine’s Department of Medical Pharmacology and Physiology and the Dalton Cardiovascular Research Center, looked at the two genetic mutations that cause specific chloride channels in the cell, known as the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels, to malfunction. This malfunction ultimately leads to repeated pneumonia, the primary cause of most deaths associated with cystic fibrosis.
“The normal function of a cell is to pass chloride ions across the cell membrane at a very fast speed,” said Hwang. “We know some signaling molecules elicit this reaction, much like a hand signals an automatic water faucet to dispense water. But in the case of cystic fibrosis, that signal is no longer detected by the mutated channel protein. Through some mechanisms we still don’t quite understand, malfunction of this channel protein eventually leads to bacterial infection in the lung, which is believed to be responsible for the most severe symptoms of cystic fibrosis.”
Hwang’s study found that manipulating the sensor of the channel protein can significantly rectify the malfunction of the mutated channel, thus opening the door to a drug design that may eventually lead to a “real cure.”
“We could help a lot of patients if we can utilize the power of computer simulations and structure-based drug design to discover new therapeutical reagents for cystic fibrosis, but it’s very expensive to do this kind of research in an academic institute,” added Hwang.