For decades, the University of Iowa has been home to some of the most significant advancements in our understanding and treatment of cystic fibrosis. A recent $3.63M/five-year grant from the National Institutes of Health to a multidisciplinary team of researchers led by Drs. David Stoltz and Joseph Zabner may lead to the next ground-breaking discovery.
Cystic fibrosis is a life-shortening lung disease, characterized by airway infection and inflammation, beginning during infancy and leading to respiratory failure. Although new therapies have reduced the suffering of people with this disease and extended their lives, preventing or reducing the initial infection could dramatically improve the course CF takes in an individual’s life. Mutations in the gene encoding CFTR, an ion-conducting channel, underlie the disease, and this impairs two critical airway host defense mechanisms: reduced airway surface liquid (ASL) antimicrobial activity and abnormal mucociliary transport (MCT).
Previous research has shown that abnormally acidic ASL affects both of these host defense mechanisms. If the ASL pH could be increased via tromethamine (THAM), the researchers argue, it is possible that the development of CF lung disease may be alleviated or prevented. The newly funded R01 grant will allow for the testing of this hypothesis. THAM, an FDA-approved alkalinizing agent, will be aerosolized in a variety of conditions to increase ASL pH in humans and pigs with CF. Positive outcomes in this study could have profound effects for treating or preventing CF lung disease.
Drs. Stoltz and Zabner’s team of researchers on this grant is composed of Internal Medicine colleagues Drs. Michael Welsh, Mahmoud Abou Alaiwa, and Lakshmi Durairaj, as well as pathologist Dr. David Meyerholz, Occupational and Environmental Health’s Dr. Peter Thorne, Dr. Eric Hoffman from the Department of Radiology, and former Internal Medicine resident and Pulmonary Fellow Dr. Pradeep Singh, now at the University of Washington. Congratulations to this team on their tremendous grant win!