A study led by a Seattle research team has shown a new drug, called ivacaftor or VX-770, significantly improves lung function and other symptoms in cystic fibrosis patients with a specific mutation.
The mutation, called G551D-CFTR, is present in only about 4 percent of cystic fibrosis patients, but the findings suggest the drug may also benefit patients with more common mutations, either alone or, more likely, in combination with other drugs, said Dr. Bonnie Ramsey, director of the Center for Clinical and Translational Research at Seattle Children’s Research Institute and lead author on the study.
The findings also suggest that even adults with long-standing disease can recover at least some lung function, Dr. Ramsey said. ”That was always a question: once you’ve had lung damage could you reverse it.”
Cystic fibrosis is the most common lethal inherited disease among whites, but occurs in other racial groups as well. About 30,000 Americans have the disease.
The disease is caused by mutations in the gene that provides cells with the instructions needed to make a protein called cystic fibrosis transmembrane conductance regulator, or CFTR.
This protein forms a channel through which chloride ions flow in and out of the cell. The protein also helps regulate the flow of sodium ions as well.
The flow of these ions, in turn, helps determine the viscosity of the mucous in the airways of the lung as well as the viscosity of secretions in other passageways, including those in the liver, pancreas, gastrointestinal tract and reproductive organs.
Mutations in the CFTR gene can have different effects. Patients in this study, for example, who have the G551D-CFTR mutation make channel proteins that do not open up properly. Ivacaftor binds to this protein and opens the channel so the ions can flow.
With other mutations, however, the malformed proteins may not even get to the cell surface or, if they do, not in sufficient numbers.
Without normally functioning CFTR proteins, a person’s secretions become thick and viscous. In the lungs, the thicker mucous blocks airways, leading to chronic lung infections and a relentless decline in lung function.
Blockages in other organ systems, such as the pancreas and liver, cause a variety of problems, including diabetes and malnutrition.
Despite advances in treatment, there is no cure and half of patients with cystic fibrosis die before age 37, most from respiratory failure.
In the new study, 161 patients age 12 or older were randomly assigned to either take ivacaftor or a placebo two times a day for 48 weeks.
At the end of the study, the researchers found that compared to those who took the placebo patients who took the drug saw their lung function improve 17 percent. They also saw a marked reduction in flares ups of respiratory symptoms and reported a general improvement in their overall health. In addition, on average, they gained more than 7 pounds over the 48 weeks of the study.
“It’s really the constellation of effects that’s impressive,” said Dr. Ramsey. “You have not only improvement of lung function, but also improved quality of life, a decrease in flare ups and a substantial weight gain.”
Trials combining ivacaftor with drugs that target other genetic defects responsible for cystic fibrosis are underway, Dr. Ramsey said.
Ivacaftor is being developed by Vertex Pharmaceuticals with financial support from the Cystic Fibrosis Foundation. The new study, which was funded by the company, the foundation and large number of government agencies, appears in the current issue of the New England Journal of Medicine.
Co-investigators in the Washington region are: Moira Aitken, MD, professor of medicine in the Division of Pulmonary and Critical Care Medicine at the University of Washington Medical Center and Ronald Gibson, MD, PhD, director of the Cystic Fibrosis Clinical Center at Seattle Children’s Hospital and professor of pediatrics at the University of Washington School of Medicine.
To learn more:
- Visit the National Library of Medicine’s Home Genetic Reference section on cystic fibrosis.
Additional information can be found on these National Library of Medicine pages.