Researchers are developing a new drug to treat severe lung damage and breathing problems in individuals with severe infections or undergoing certain cancer treatments.
Scientists at Cincinnati Children’s Hospital Medical Center report April 19, 2016 in Science Signaling that a transcription factor called FOXF1 activates several biological processes that promote recovery from acute lung injury. Two laboratories at Cincinnati Children’s are developing a pharmacologic compound that in mouse models stimulates FOXF1 and promotes repair after lung injury.
“Besides toxic insults from some cancer treatments, acute lung injury can be a major medical problem for people who get infectious diseases like flu, pneumonia or Ebola because of pathogens that target the lung,” said Vladimir Kalinichenko, MD, PhD, co-senior author and a physician and researcher in the Divisions of Pulmonary Biology and Developmental Biology at Cincinnati Children’s. “A small molecule compound we developed efficiently stabilizes the FOXF1 protein in cell cultures and mouse lungs, and it shows promise in inhibiting lung inflammation and protecting experimental mice from lung injury.”
Along with co-senior author Tanya Kalin, MD, PhD, in the Cincinnati Children’s Perinatal Institute, the research team learned that loss of FOXF1 in lung endothelial cells of mice caused them to die from respiratory problems, pulmonary edema (fluid in the lungs) and lung inflammation. This happens when endothelial cells that line blood vessels in the lung can no longer provide a protective barrier between the external environment and the body’s circulatory system.
Mutations in FOXF1 gene cause alveolar capillary dysplasia, a rare and universally fatal congenital lung disorder of newborns and infants that researchers said underscores the importance of the FOXF1 in the respiratory system. Alveolar are tiny air sacs in the lung.
The authors propose that stabilizing or restoring FOXF1 will promote the formation of blood vessels in lungs, promote healing and decrease breathing complications in children and adults.
Photo Credit: Cincinnati Children’s