Tamorah R. Lewis, MD, PhD
Neonatologist; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of MedicineFull Biography
William Truog, MD
Director, Center for Infant Pulmonary Disorders; Sosland Chair in Neonatal Research; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Professor of Pediatrics, University of Kansas School of MedicineFull Biography
Tamorah Lewis, MD, PhD, and William Truog, MD, Neonatology, were recently awarded a two-year, $455,856 R21 grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, one of the National Institutes of Health in the United States Department of Health and Human Services.
Drs. Lewis and Truog’s project is called “Less Lumping, Smarter Splitting: Genomics and Metabolomics of Systemic Steroid Response in Bronchopulmonary Dysplasia.” It will assess genomic and metabolomic markers which correlate with steroid response in a group of preterm infants who have evolving Bronchopulmonary Dysplasia (BPD).
As the two explained in their project summary, 2.5 million infants are born at less than 32 weeks gestation worldwide every year, with approximately 75,000 of them born in the U.S. Many of these preterm infants develop the severe form of lung disease BPD and have poor lung function. The longer-term effects can be everything from prolonged oxygen therapy to increased morbidity after common lung infections. One commonly used drug therapy for BPD is systemic steroids, which produces variable and unpredictable short-term pulmonary benefit, but are also associated with neurodevelopmental impairment and other side effects such as growth stunting, hypertension and decreased bone mineralization.
“Given the inconsistency in producing intended clinical results and high risk for adverse effects, it is important to identify a group of infants with BPD who will benefit the most from steroid therapy,” Drs. Lewis and Truog wrote. “There are functionally important genetic variants known to impact steroid metabolism and response in similar patient populations, so we know that variability in steroid response likely has, in part, genetic underpinnings.”
The goal of the study is to make clear the genomic and metabolomics biomarkers of clinical response as a mechanism to identify a group of infants with the most favorable risk-to-benefit-ratio, thus moving the field of BPD treatment towards precision medicine. By better understanding steroid response variability, the team hopes to move BPD therapy into the age of personalized therapeutics in this group of infants.
“The proposed research is significant because pharmacogenomics and pharmacometabolomics have the potential to shift the paradigm from largely unexamined 20th Century population-based dosing regimens, with little account for patient inter-individual variability, towards a Precision Medicine approach,” the two wrote. “We will use contemporary tools (genomics, metabolomics) to identify infants with the greatest likelihood of therapeutic benefit with the naturally associated minimization of development of adverse events by preventing steroid exposure to infants unlikely to respond. This precision therapeutics approach addresses a large gap in current knowledge and can lead directly to improved pharmacotherapy for infants with BPD.”
Drs. Lewis and Truog used the mechanism of being multiple Principal Investigators for this grant. Other sites that will recruit infants for this study are the Children’s Hospital of Philadelphia and Nationwide Children’s Hospital.