Infants who are born very prematurely are at risk for abnormal lung development and lung injury, a condition called bronchopulmonary dysplasia (BPD). Severe BPD can cause pulmonary hypertension (high blood pressure in the lungs) leading to right heart failure. No therapeutic agents have been rigorously tested for prevention or treatment of this life-threatening condition, which affects an estimated 10,000 to 15,000 infants in the United States every year.
Enter physician-scientist Judy Aschner, M.D., member scientist at the Hackensack Meridian Center for Discovery and Innovation (CDI) who has received a federal grant to investigate an amino acid which has shown promise in improving the condition in preclinical models.
The roughly $470,000 National Heart, Lung, and Blood Institute funding will cover the first planning year of a four-year R61/R33 grant proposal to study the amino acid L-citrulline, a substrate which drives nitric oxide production, in preterm infants requiring breathing support in the neonatal intensive care unit (NICU).
During the three-year R33 implementation phase, preterm infants who are at high risk for BPD and pulmonary hypertension (BPD-PH) will be enrolled from four NICUs around the country, including from the Joseph M. Sanzari NICU at HUMC, in a multi-dose, blinded, and placebo-controlled study to demonstrate the safety profile and study the uptake and metabolism (pharmacodynamics) of L-citrulline administration in this vulnerable population. A third exploratory aim is to evaluate the clinical efficacy and identify the optimal dose of L-citrulline for a future Phase 3 efficacy randomized controlled trial of L-citrulline to prevent BPD-PH in preterm infants.
“This study has the potential to improve outcomes for preterm infants by advancing the study of L-citrulline as a therapy to prevent or ameliorate a devastating disease process in an understudied population of patients in desperate need of new treatments,” according to Aschner and team.
Aschner is a pediatrician, neonatologist and health care leader. She and her colleagues have been studying the mechanisms of action and potential therapeutic value of L-citrulline for neonatal lung disease for the past two decades. She is widely known for her work with the national ongoing Environmental Influences on Child Health Outcomes (ECHO) program, a massive national cohort started in 2016 and renewed in 2023. A five-year, $27 million grant was awarded to Aschner last year to continue her ECHO work.