Elizabeth Perkett, M.D., examines patient Andrea Vaccarell, 12, at the Monroe Carell Jr. Children’s Hospital at Vanderbilt cystic fibrosis clinic. (photo by Neil Brake)
Cystic fibrosis study takes new approach
A pediatric lung expert who recently returned to the Monroe Carell Jr. Children's Hospital at Vanderbilt to expand its cystic fibrosis (CF) program is bringing with her a potential new approach for treating the disorder.
Elizabeth Perkett, M.D., professor of Pediatric Pulmonology, is the principal investigator of a study of a drug — hydroxychloroquine — that she theorizes may play a role in preventing cystic fibrosis damage in the lungs by normalizing pH levels.
The study is based on research Perkett conducted during her seven-year stint at the University of New Mexico prior to returning to Vanderbilt.
“For years we have been looking at the chloride exchange, or salt exchange, of the lungs in CF patients, but that hasn't led to many new treatments,” Perkett said. “I applied findings from my first time around here at Vanderbilt regarding transforming growth factor beta (TGF-B) in lung cells with new insights related to organelle acidification discovered by Dr. Vojo Deretic at the University of New Mexico.”
That research is detailed in November's Journal of Clinical Investigation entitled “Elevated furin levels in human cystic fibrosis cells results in hyper susceptibility to exotoxin A- induced cytotoxicity.” The study details evidence for the use of pH regulatory drugs to treat cystic fibrosis (CF).
“We hypothesized that this could point to a new path for treatment. This is the first time we have looked this deeply into the possibility of controlling intracellular acidity to improve the health and lifespan of cystic fibrosis patients.”
Perkett and adult CF clinic colleagues Bonnie Slovis, M.D., and Bryan Williams, M.D., enrolled 20 patients in the Vanderbilt study.
Perkett's lab research suggests the use of hydroxychloroquine to normalize the pH in lung cells may reduce fibrosis, make the lung tissue less sticky and less susceptible to pseudomonas, which should ultimately decrease inflammation in the lungs of CF patients.
In addition to examining standard measures of lung function, including spirometry and bacterial cultures, the study will be using a new research tool: exhaled breath condensate. It has been shown that the pH in exhaled breath condensate from CF patients is more acidic, so the pilot study will help determine whether hydroxychloroquine treatment changes the airway pH to normal, a possible indication that pH within the cells is normalizing as well.
Perhaps most exciting of all is the fact that hydroxychloroquine is a medication already used in a number of inflammatory diseases, including lupus, pulmonary fibrosis and rheumatoid arthritis. That means if it works, it could be available to CF patients much more quickly than if a new drug were being developed.
Perkett plans to have a much more active basic science and clinical research program dedicated to cystic fibrosis at Vanderbilt.
Research to determine if correcting intracellular pH can extend the lives of CF patients is an exciting way to start, she said.