Protein Linked to Lung Development Identified

Finding might lead to new treatments for premature infants in respiratory distress

FRIDAY, Sept. 22, 2006 (HealthDay News) -- Research that uncovers a protein pathway critical to lung development holds the promise of new treatments for premature babies who suffer from respiratory distress syndrome.

"There is a lot of work that must be done, but at least we have a new set of molecules for which, if a receptor is found, intervention is possible," said study author Vrushank Dave, an assistant professor of pediatrics at University of Cincinnati Medical Center.

"This is the first signaling pathway that has been identified for lung maturation," Dave said. In their research, which is published in the Sept. 21 online issue of the Journal of Clinical Investigation, his team found the protein calcineurin is necessary for lung tissue development at birth.

The study was performed in fetal mice and identified a specific signaling pathway for genes that controlled how lung tissue developed. That's good news because until now, the controlling proteins for the final stages of lung development have not been identified.

"It is critical to understand that this work was done in mice, so we can't make a blanket statement saying that the (research) will translate into humans," Dave cautioned.

Still, the animal work is important because right now, there's no definitive treatment for premature babies who develop respiratory distress syndrome, Dave noted. Lungs fully develop very late in pregnancy, so premature infants are at risk for lung disease when they're born. Currently, mothers at risk for preterm delivery are given a single shot of a corticosteroid to help reduce the chances of their babies developing these conditions.

"Prenatal corticosteroids for the prevention of respiratory distress syndrome improves lung maturation; it has some confounding problems," Dave said. These infants are at a very high risk of dying, despite aggressive treatment that can include a mechanical respirator.

Almost one-fourth of premature infants develop respiratory distress syndrome because the cells that line their lungs are not fully developed, so they can't breathe properly; about 60,000 children in the United States are born each year weighing less than three pounds. Of those who survive, many suffer permanent lung damage, which can slow growth, increase the possibility of infection, and result in abnormal brain development.

The current study sheds some much needed light on the syndrome. The researchers deleted the calcineurin b1 gene in the respiratory cells of fetal mice, which stunted lung maturation and caused respiratory failure. The gene deletion decreased the synthesis of surfactant and other proteins necessary for lung development. Because they lacked the protein calcineurin, the newborn mice could not breathe properly and died soon after birth, the researchers wrote.

The mouse research may apply to premature infants because "failed lung maturation at birth results in surfactant deficiency, causing respiratory distress in the perinatal period," the authors wrote.

Future treatment will hinge on more basic science. "The idea is to find the receptor for the [calcineurin] pathway, and we don' have it at this point," Dave said.

The hope is that the description of this pathway that controls the final stages of lung development in mice might help researchers design treatments to manage respiratory distress syndrome and lung disease in premature babies.

Once the receptor is found, "we would like to find molecular targets for the receptor. If we can find that receptor, then it would be possible to see how much we can increase lung maturation," Dave said.

Finding a receptor for the pathway would activate it, but "that's not only the pathway involved. This is very complex phenomenon -- in the last few days before birth, a lot of structural and functional changes in lung are going on," he explained.

This research, Dave stressed, is in its infancy. "We don't know the therapeutic target. This (approach) would work if there's a defect in the receptor pathway, but if there's a cellular defect, that can't be cured with this research," he said.

More information

For more on acute respiratory distress syndrome, go to the American Lung Association.

SOURCES: Vrushank Dave, Ph.D., University of Cincinnati Medical Center, Cincinnati, Ohio; Sept. 22, 2006, Journal of Clinical Investigation
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