Grant: Project Grant

About 1,500 babies are born extremely premature in Canada each year. Advances in medical care over the last 20 years have improved the survival of these babies, but in about half at the cost of a severe injury to the lung called bronchopulmonary dysplasia (BPD). Babies with BPD suffer from a permanent interruption of normal lung development; therefore, they carry their lung disease with them their entire lives and in the most severe cases die before school age. Medical costs related to BPD are among the highest for all childhood diseases, being second only to asthma. Preventing disease due to prematurity is therefore of critical importance to the health of Canadians. The proposed experiments will use animals with experimental BPD and lung tissues from human newborn infants to define and confirm the involvement of specific pathways leading to lung injury: Rho-kinase (ROCK) and thrombospondin (TSP)-1. We will give a promising class of drug by inhalation, known as a ROCK inhibitor, to determine safety and efficacy in rats with BPD. Another molecule regulated by ROCK is TSP-1, which our work suggests is critical to interruption of normal lung development. Importantly, we will allow rats to grow into adults to see whether benefits of targeting ROCK and TSP-1 are long-lasting. Our group is uniquely equipped with the facilities and expertise to perform the experiments that are proposed. In particular, ours is the only group possessing the ability to perform precise measurements of lung structure using a technique called "unbiased stereology". Collectively, these experiments represent a critical step toward the translation of novel drugs targeting molecules implicated in BPD, which could represent a breakthrough in our ability to improve health outcomes among Canadians who were born premature.