Researchers' new test for cystic fibrosis may lead to more treatments

Treatments for cystic fibrosis may be faster to develop with the use of a new test created by Stanford researchers.

The test, which involves sampling sweat, shows that people need smaller amounts of a particular protein function than previously thought to avoid cystic fibrosis symptoms, according to Jeffrey Wine, PhD, a professor of psychology and of biology.

"I was amazed it worked out as well as it did," said Wine, who also is director of Stanford's Cystic Fibrosis Research Laboratory and a member of the Child Health Research Institute at Stanford. Wine and his colleagues, including faculty in the School of Medicine, used the test to measure levels of protein function in patients taking a cystic fibrosis drug. Their findings were published Feb. 10 in PLOS ONE. Wine was the senior author of the study. The lead author was Jessica Char, a life science research assistant.

Cystic fibrosis is a recessive genetic disorder that disables a key protein — known as the cystic fibrosis transmembrane conductance regulator, or CFTR — that is responsible for transferring fluid and minerals in and out of cells.

The effect on the 30,000 Americans diagnosed with the condition is debilitating: They suffer from chronic lung infections, male sterility and a host of other symptoms. In the past, carriers struggled to survive past infancy.

Doctors usually treat cystic fibrosis by tackling symptoms as they appear. Very few drugs target the underlying problem — that is, patients' broken, damaged or missing CFTR.
CFTR defects vary greatly: The entire protein might be missing, or it could have just a few flaws. Current tests, which measure the amount of chloride in sweat, can't precisely identify how much functioning CFTR is present.

The new test determines the ratio between the volumes of two types of sweat in each individual by using dyes to color sweat bubbles that form on the skin, revealing the individual's level of CFTR function.

Wine's work showed that even healthy people have varying levels of CFTR function and that only a small amount of CFTR is needed to remain disease-free. "The biggest surprise for me was how small the response was," Wine said. "I don't think anybody expected that."

Therefore, drug developers have a lower target: They would need to restore less than 10 percent of CFTR functionality to improve symptoms, based on the researchers' findings.

The researchers examined the CFTR function in eight subjects with cystic fibrosis. Six of the patients were taking ivacaftor, a drug currently available to treat some types of cystic fibrosis. (Ivacaftor boosted CFTR function as expected, and also increased CFTR function in a type of cystic fibrosis it is not currently designed to treat, Wine said.)

Next, Wine said, he plans to examine differences in CFTR in healthy individuals. He hopes eventually to determine the precise amount of CFTR needed to alleviate symptoms.

"The CF community is eagerly awaiting these CFTR-directed therapies," Wine said. "We are trying as hard as we can to speed drug delivery to patients."

Other Stanford co-authors are former research assistant Marlene Wolfe; postdoctoral scholars Hyung-ju Cho, MD, PhD, Il-Ho Park, MD, PhD, and Jin Hyeok Jeong, MD, PhD; visiting scholar Eric Frisbee; clinical research coordinators Colleen Dunn and Zoe Davies; Carlos Milla, MD, associate professor of pediatrics; Richard Moss, MD, professor emeritus of pediatrics; and Ewart Thomas, PhD, professor of psychology.

The study was supported by a grant from Cystic Fibrosis Foundation Therapeutics.