New test for cystic fibrosis may lead to more treatments

February 12, 2014 by Becky Bach
Stanford researchers have created a new test for people with cystic fibrosis, who suffer chronic lung infections. Credit: Kozorez Vladislav/Shutterstock

(Medical Xpress)—Treatments for cystic fibrosis may be easier to develop with the use of a new test created by Stanford researchers.

The test – taken by sampling sweat – shows that smaller amounts of a particular protein are necessary to stop symptoms than previously thought, according to Jeffrey Wine, a professor of psychology and biology who is the director of Stanford's Cystic Fibrosis Research Laboratory.

"I was amazed it worked out as well as it did," Wine said. Wine and colleagues in the Stanford School of Medicine described the test in October in the journal PLoS ONE. Since then, they have used the test to measure protein levels in patients taking a cystic fibrosis drug. That research has now also been published in PLoS ONE.

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.

Wine knows the cost of the disease firsthand: his 32-year-old daughter, Nina, has cystic fibrosis. She's been lucky so far and is healthy enough to run marathons and pursue a master's degree in global health, Wine said. But she relies on a cocktail of drugs to maintain her health.

Doctors usually treat cystic fibrosis by tackling symptoms as they appear. Very few drugs target the underlying problem: a patient's CFTR is broken, damaged or missing.

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 determines the ratio between two types of sweat in each individual by using dyes to form bubbles on the skin. That ratio accounts for differences in sweat volume – between a conditioned athlete and a sedentary person, for example – and reveals an individual's CFTR levels.

Wine's work showed that even healthy people have varying levels of CFTR 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. I don't think anybody expected that," Wine said.

Therefore, drug developers have a lower target: they only need to restore 10 percent of CFTR functionality to relieve symptoms. Also, patients can be treated with drugs that supplement their personal CFTR levels to relieve symptoms. That is particularly important because people with the same genetic flaw can have different amounts of CFTR, Wine said.

The researchers, who include lead author Jessica Char, a research assistant in Wine's group, examined the CFTR levels 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 levels as expected, but it also increased CFTR levels 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.

"(My daughter) would really love to have a drug," Wine said.

Explore further: Insights into a new therapy for a rare form of cystic fibrosis

More information: Wine JJ, Char JE, Chen J, Cho H-j, Dunn C, et al. (2013) "In Vivo Readout of CFTR Function: Ratiometric Measurement of CFTR-Dependent Secretion by Individual, Identifiable Human Sweat Glands." PLoS ONE 8(10): e77114. DOI: 10.1371/journal.pone.0077114

Char JE, Wolfe MH, Cho H-j, Park I-H, Jeong JH, et al. (2014) "A Little CFTR Goes a Long Way: CFTR-Dependent Sweat Secretion from G551D and R117H-5T Cystic Fibrosis Subjects Taking Ivacaftor." PLoS ONE 9(2): e88564. DOI: 10.1371/journal.pone.0088564

Related Stories

Insights into a new therapy for a rare form of cystic fibrosis

October 29, 2012
Scientists at the Hospital for Sick Children in Toronto have established that a drug recently approved by the U.S. Food and Drug Administration to treat a rare form of cystic fibrosis works in an unconventional way. Their ...

New insights into functionality of cystic fibrosis protein

September 26, 2012
CFTR is an important protein that, when mutated, causes the life-threatening genetic disease cystic fibrosis. A study in The Journal of General Physiology (JGP) details how an accidental discovery has provided new understanding ...

Cystic fibrosis: New compounds display strong therapeutic potential

September 30, 2013
Cystic fibrosis is a lethal genetic disorder that in France affects one child per 4,500 births. An international team led by scientists at the Institut Fédératif de Recherche Necker-Enfants Malades (CNRS/Inserm/Université ...

An 'unconventional' path to correcting cystic fibrosis

September 1, 2011
Researchers have identified an unconventional path that may correct the defect underlying cystic fibrosis, according to a report in the September 2nd issue of the journal Cell. This new treatment dramatically extends the ...

U of T and SickKids first to grow lung cells using stem cell technology

August 29, 2012
Researchers at the University of Toronto and the Hospital for Sick Children (SickKids) are paving the way towards individualized medicine for patients with cystic fibrosis. 

Computer-designed molecules point to new therapy for cystic fibrosis

April 19, 2012
By developing software that uses 3-D models of proteins involved in cystic fibrosis, a team of scientists at Duke University has identified several new molecules that may ease the symptoms of the disease.

Recommended for you

Link between cells associated with aging and bone loss

August 21, 2017
Mayo Clinic researchers have reported a causal link between senescent cells - the cells associated with aging and age-related disease - and bone loss in mice. Targeting these cells led to an increase in bone mass and strength. ...

Gut microbes may talk to the brain through cortisol

August 21, 2017
Gut microbes have been in the news a lot lately. Recent studies show they can influence human health, behavior, and certain neurological disorders, such as autism. But just how do they communicate with the brain? Results ...

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.