This week, a team of interdisciplinary researchers led by Dr. Joseph Zabner, MD, of the University of Iowa’s Carver College of Medicine, published a study that provides evidence for the therapeutic repurposing of tromethamine, a drug used to treat electrolyte imbalance, for patients with cystic fibrosis (CF).
The study, “Repurposing tromethamine as inhaled therapy to treat CF airway disease,” was published in the latest online edition of the Journal of Clinical Investigation.
According to Zabner and his colleagues, mammalian airways evolved with a thin layer of fluid called airway surface liquid (ASL) that is rich in immunological defense mechanisms. The lung’s ASL volume, pH, and electrolyte composition are crucial for proper immune system functioning. In a disease such as CF, there is a distinct dysfunction of these crucial elements, especially the critical electrolyte and pH, so it is harder for these patients to fight off respiratory infections.
To test whether tromethamine, a drug used to treat metabolic electrolyte imbalance, could also have a successful therapeutic impact on CF patients, the researchers utilized both an animal model (pigs) of CF and clinical patients with the disease to test their hypothesis. They examined the effect of tromethamine on the immunologic response of animals and patients and found that tromethamine, either alone or in combination with a saline solution, might be a therapeutic benefit in CF airway disease.
“In this study, we identified an FDA-approved i.v. buffer that might be repurposed as an aerosol to alkalinize the ASL of CF airways,” the researchers wrote about their findings. “Loss of CF transmembrane conductance regulator reduces airway epithelial HCO3–secretion, diminishes ASL pH, and interferes with at least two important host defenses: antibacterial activity and mucociliary transport. Each defect may independently contribute to lung disease in CF.
“Treating people with CF with antibiotics improves their clinical status, without correcting the mucus abnormalities,” the authors added. “Accordingly, inhaled tromethamine might be beneficial, even it only corrects the antimicrobial defect. While increasing ASL pH will change the viscoelastic properties of CF mucus, it is unclear whether such changes in pH and viscosity would enhance mucus clearance.”