Scott H. Donaldson, MD, Professor of Medicine in the Division of Pulmonary and Critical Care Medicine is first author on a new study that shows restoring the activity of the cystic fibrosis transmembrane conductant regulator (CFTR) using the therapeutic agent Ivacaftor can lead to significant improvements in physiologic assessments.
Cystic fibrosis is caused by various mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Loss of CFTR function is the basis of CF because protein acts as a channel across the membrane of cells that are specialized to produce mucus, sweat, saliva, tears and digestive enzymes.
In this recent study published in the Journal of Clinical Investigation Insights, Donaldson performed a multisite, prospective, observational study of ivacaftor, prescribed in patients with the G551D-CFTR mutation. Measurements of lung mucociliary clearance (MCC) were performed before and after treatment initiation (1 and 3 months), in parallel with clinical outcome measures.
Results showed that using Ivacaftor, a highly effective CFTR modulator, used in a responsive population greatly improved mucociliary clearance, which is believed to be the link between CFTR mutations and the development of CF lung disease. Because improvement in MCC was also correlated with clinical lung function measurements (FEV1) in individual subjects, this MCC biomarker might be useful to identify other CFTR modulators that improve CF lung disease.
“Restoration of CFTR activity with ivacaftor led to significant improvements in MCC, and this physiologic assessment provides a means to characterize future CFTR modulator therapies, as well as predict improvements in lung function,” Donaldson said.
“We anticipate that additional CFTR restoring therapies will be approved within the next year, bringing highly active therapies to about 90% of patients. We also expect that this will bring a tremendous change to clinical outcomes.”
Co-investigators included Beth L. Laube, PhD (Professor, Pediatrics, Johns Hopkins University), Timothy E. Corcoran, PhD (Associate Professor of Medicine and Bioengineering; University of Pittsburgh); Pradeep Bhambhvani, MD (Professor, Division of Molecular Imaging and Therapeutics, UAB); Kirby Zeman, PhD (Center for Environmental Medicine, Asthma, and Lung Biology, UNC), Agathe Ceppe, MS (Marsico Lung Institute, UNC); Pamela L. Zeitlin, MD (Professor of Pediatrics; National Jewish Health); Peter J. Mogayzel, Jr., MD, PhD (Professor of Pediatrics; Johns Hopkins University); Michael Boyle, MD (Adjunct Professor of Medicine; Johns Hopkins); Landon W. Locke, PhD (Department of Microbial Infection and Immunity; Ohio State University); Michael M. Myerburg, MD (Associate Professor of Medicine; University of Pittsburgh); Joseph M. Pilewski, MD (Professor of Medicine; University of Pittsburgh); Brian Flanagan (UAB); Steven M. Rowe, MD (Professor of Medicine, UAB); and William D. Bennett, PhD (Professor of Medicine, UNC).
Therapies like Ivacaftor are currently being developed to restore various levels of CFTR function, depending upon the specific gene mutation the patient possesses. Approximately 1,700 individual mutations in the CFTR gene can cause CF.