Researchers at the Salk Institute for Biological Studies have identified a new form of respiratory distress syndrome (RDS) in newborn mice, tracing the problem to a cellular receptor for thyroid hormone—a key player in many developmental processes in the body. The researchers also found that two drugs used for treating overactive thyroid glands saved mice with a deadly genetic alteration that mimicked the newly discovered lung problem.

“We’ve added a piece of the puzzle that had been missing for decades,” said Ronald Evans, an investigator with the Howard Hughes Medical Institute and the March of Dimes Chair in Developmental and Molecular Biology at Salk. “This gives us an entirely new avenue for explaining and treating RDS and other respiratory problems that occur in infants.”

The disease, which occurs because the infants’ lungs are not yet fully developed at birth and lack the surfactant necessary for the lungs to inflate with air, is often treated with glucocorticoids, given to expecting mothers and premature infants. The glucocorticoids speed maturation of type 2 pneumocytes—surfactant-producing cells. In some cases, however, infants fail to respond to the steroid treatment, and die from RDS, suggesting that some other biological mechanism might be at work.

To explain this, the Salk team turned their attention to another type of cell lining the lungs, type 1 pneumocytes, flat cells that allow air exchange between the blood stream and the lung’s interior. The researchers knew that both types of cells—type 1 and type 2 pneumocytes—are important to lung development, and while type 2 cells are well understood, little is known about type 1 cells.

For the study, the researchers developed a strain of mice in which they disrupted the ability of type 1 pneumocytes to respond normally to thyroid hormone, which prevented the cells from maturing. Unlike type 2 pneumocytes, which mature rapidly in infants given steroid hormone, the type 1 cells failed to respond to steroid treatment and the mice died due to the inability of their lungs to function.

However, mice treated with the medications propylthiouracil or methimazole, normally given to people with thyroid disease, recovered from the disorder and their type 1 cells matured normally.

“This might explain why some infants don’t respond to steroid treatment, which only targets the type 2 pneumocytes,” said Evans. “There may be an entirely different underlying problem than what the doctor is treating.”

Since he genetic make up of mice and human is very similar, the researchers are optimistic that their findings will eventually lead to new treatments for infants with RDS. They also believe that the discovery of this mechanism could help play a role in healing lung tissues in older children and adults who have suffered lung damage from flu, asthma, emphysema, or other types of respiratory disorders.

The researchers caution, however, that the thyroid drugs used in this study are only approved for adults, and their use in infants would have to be explored with caution.

Their findings appear in the journal Nature Medicine.

Source: Salk Institute for Biological Studies