Grant: Collaborative Health Research Projects

Preterm birth (PTB) is the leading cause of newborn death and the second leading cause of child death. Children bornpreterm often have lifelong health issues, including cerebral palsy, cognitive impairement, blindness, deafness, respiratoryillness and gastrointestinal disorders, as well as chronic diseases such as hypertension and dyslipidemia. Hospital costsassociated with PTB are among the most expensive: premature babies remain hospitalized an average of 11 days longer ata higher cost compared to term births; newborns born prior to 28 weeks gestation incur major costs (~$100,000/infant). Inspite of a better understanding of risk factors and mechanisms related to premature contractions, and the introduction ofpublic health prevention programs, the rate of PTB has increased. The economic implications of PTB make it the most costlymedical urgency per patient. These statistics demonstrate that significant savings could be obtained by the development ofeffective treatments, which can prolong gestation, so called tocolytic agents. Prostaglandin-F2alpha (PGF2alpha) initiateslabour, induces childbirth, and works in compliment with the small peptide hormone oxytocin, which is commonly used toinduce labor in humans. Towards the development of a new tocolytic agent, we targeted the PGF2alpha receptor (FP) fortwo specific reasons: 1) FP expression increases during the initial phase of parturition, and 2) FP ''knock-out'' mice do not gointo labour and must be delivered by cesarian. By creating a series of novel modulators, including peptide-based analogsproving successful in clinical studies, we have validated FP as a viable target. The proposed research is designed to furtherdevelop our prototypes to provide basic knowledge of the role of FP in parturition, to train highly qualified personnel ininterdisciplinary research, and to develop effective therapy to treat preterm labour (PTL) to enhance quality of life from birthwhich impacts throughout life.