After almost a decade of research, neonatal experts believe an existing arthritis drug may be able to reduce the impact of bronchopulmonary dysplasia (BPD) by triggering the natural antioxidant defense system in the lungs, according to researchers.
BPD mostly affects premature infants who are born more than ten weeks before their due date, weigh less than two pounds, and have breathing problems that require oxygen therapy.
“Babies lungs aren’t physiologically ready for room air until they are at least 35 weeks old. We give pre-term infants medicines along with supplemental oxygen that allows them to breathe, and these interventions have saved hundreds of thousands of lives,” said Trent Tipple, MD, a BPD researcher in the Center for Perinatal Research at NCH. “But the interventions come with a cost. Infant’s lungs are forced to process oxygen weeks before they develop the ability to do so and weeks before natural protective antioxidant responses are in place.”
Through studies, Tipple noted that numerous cancer studies showed tumor cells thrived in a low oxygen environment, but in a hyperoxic, or high oxygen environment, tumor cells grew more slowly. Cancer researchers attributed this process, in part, to a specific tumor growth pathway regulated by the protein thioredoxin (Trx).
Through a number of mouse studies, Tipple’s team learned that neonatal lungs might also use the Trx system to regulate growth, and that the function of the protein is directly related to changes in oxygen levels, transmitting signals to the genes that instruct them to stop lung development.
The team showed that adult mice treated with an inhibitor of the Trx system, called aurothioglucose (ATG), had less lung injury when exposed to high oxygen levels. ATG has been used for decades as a rheumatoid arthritis treatment.
“Currently we are researching the optimal dose of ATG in a BPD mouse model, looking at how Nrf2 is activated and seeing if we can reduce the severity of oxygen-induced lung injury,” said Tipple. “Our preliminary findings are very promising. We’re also investigating ATG’s potential to protect other organs like the brain that are negatively impacted by oxygen therapy.”
