Grant: Project Grant

Congenital diaphragmatic hernia (CDH) happens during fetal development, when a hole in the diaphragm causes structural changes in the lungs, leading to lifelong challenges with breathing. In Canada, >20% of babies born with CDH die during or shortly after delivery. In lower-resourced countries, this proportion is much higher. Currently, there is no cure for CDH. The only treatment is surgery after delivery. The surgery is expensive, available in only a few healthcare centres worldwide, and does not fix the lung problems. We showed that a molecule called miR-200b improves lung development in a preclinical model of CDH. We think that these positive effects mean that miR-200b can treat CDH fetuses, but we need to find a way to deliver it safely. In this project, we will determine if we can deliver miR-200b specifically to the developing fetal lungs during pregnancy. We will deliver miR-200b with small carriers called nanoparticles. We chose nanoparticles because we can design them to deliver miR-200b only to fetal tissue and not anywhere else in the body. Our research activities will determine what the compositions of the nanoparticles should be, how well they deliver miR-200b, and if they safely and effectively improve lung development. Our experiments will use human placental cells and a preclinical model of CDH. In the shorter-term, our results will provide the proof that it is possible to use miR-200b in nanoparticles to treat abnormal lung development in CDH before birth. Over the longer-term, our research has the potential to revolutionize care for babies with CDH, in Canada and worldwide. A new treatment will improve the health and quality of life for babies with CDH and their families.