Despite the rise in illness and deaths among pregnant people, these individuals remain excluded from most clinical drug development and therapeutic trials. In response, a research team at The Ohio State University Wexner Medical Center and College of Medicine has received $4.5 million from the National Institutes of Health to develop a translational research resource platform to monitor the effects of therapeutics on placental health in pregnancy.
“More than 80% of pregnant people are exposed to or use a medication during their pregnancy, and up to 50% use three or more medications,” said one of the study’s investigators Kara Rood, MD, maternal fetal medicine physician at Ohio State Wexner Medical Center and associate professor in obstetrics and gynecology. “However, most of these drugs have not been studied specifically in pregnant people despite the unique physiologic changes that occur in pregnancy. Current practices have been hindered by many barriers including the lack of effective biomarkers and innovative study designs. There is a need to develop novel placental-specific biomarkers to assess placental function and response to therapeutics to inform their safety and efficacy.”
An example of these novel biomarkers is placental specific extracellular vesicles (exosomes) circulating in the pregnant parent’s blood. Recent advances in characterizing the cargo content of these specific extracellular vesicles demonstrated their potential to be used as placental biomarkers.
“Our goal is to develop a novel platform using exosome profiling, as novel biomarkers, to monitor the development of placental mediated adverse pregnancy outcomes and placental response to therapeutics”, said principal investigator Maged Costantine, MD, division director of maternal fetal medicine at Ohio State Wexner Medical Center and a professor of obstetrics and gynecology.
The platform will support activities of the Pediatric Precision in Therapeutics program, which is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and it will be available to the scientific community.
The study will enroll pregnant individuals at risk for preeclampsia—a leading cause for pregnancy-related illness and death. Participants receive aspirin for preeclampsia prevention and investigators will determine the effects of aspirin intake and dosage on the proteome profile of placental specific exosomes and correlate that with clinical outcomes and other biomarkers associated with preeclampsia.
The project is a collaboration between the Ohio State Wexner Medical Center and the University of Texas Medical Branch (UTMB), Galveston, including investigators with transdisciplinary and complimentary expertise in maternal fetal medicine, exosome biology, pharmacology and biomedical informatics. In addition to Costantine and Rood, the platform will be led by a multidisciplinary team at Ohio State, including Brian Searle, Damien Wilburn and Mitch Phelps, and Ramkumar Menon at UTMB as co-principal investigator with his team in exosome biology.
“When completed, the platform will establish a new model to study placental response to therapeutics in pregnancy using exosomes. This will lead to a paradigm shift in our approach to therapeutics research in pregnancy,” said Mark Landon, MD, chair of obstetrics and gynecology at Ohio State. “This can then be used to study additional therapeutics for other indications in pregnancy.”