Drug Reverses Lung Damage in Mice

Published April 19, 2016
Science Signaling

Researchers here have developed a compound that appears to reverse often-fatal lung damage.

The findings, published April 19, 2016, in Science Signaling, eventually could improve treatments for pneumonia caused by various types of infection, or in premature infants with underdeveloped lungs, and people undergoing certain cancer treatments.

The study’s leading co-authors were Vladimir Kalinichenko, MD, PhD, of the Divisions of Pulmonary Biology and Developmental Biology, and Tanya Kalin, MD, PhD, of the Perinatal Institute.

Their team analyzed mice bred with lungs lacking the transcription factor FOXF1. This resulted in abnormal endothelial cells lining the lungs’ blood vessels, which in turn made the lungs prone to deadly levels of inflammation and fluid build-up.

However, a compound that simulates FOXF1 promotes recovery from lung injury, according to the new study.

“The small molecule compound we developed stabilizes the FOXF1 protein in cell cultures and mouse lungs, and shows promise in inhibiting lung inflammation and injury,” says Kalinichenko.

The new findings are important because acute respiratory distress syndrome—a complication of lung injury—carries a 35 percent mortality rate. It accounts for about 75,000 deaths and 3.5 million hospital days each year in the United States.

“Given the lack of major improvements in the clinical management of acute lung injury and respiratory distress, there is a compelling need for innovative molecular approaches that complement existing therapies,” Kalin says.

Researchers will need to conduct much more work to prepare the compound for human clinical trials. If proven safe and effective, the compound may be useful in treating lung damage from a wide range of conditions.

Fig A:  Conceptual model depicting key elements of the family's experience with the hospital-to-home transition.
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Citation

Cai Y, Bolte C, Le T, Goda C, Xu Y, Kalin TV, Kalinichenko VV. FOXF1 maintains endothelial barrier function and prevents edema after lung injury. Sci Signal. 2016 Apr 19;9(424):ra40.

A photo of Tanya Kalin.

Tanya Kalin, MD, PhD