Grant: Catalyst Grant: Catalyzing Innovation in Preterm Birth Research

Pre-eclampsia, a high blood pressure disorder in pregnancy, has been increasing in frequency over the last thirty years. It is also one of the leading causes of premature birth and poor outcome for babies and mothers in Canada and worldwide. Treatment using various types of medications has not been successful and as such, there is no agreed upon strategy for prevention or treatment of pre-eclampsia; the only effective treatment for this disorder is delivery which leads to the premature births. In pre-eclampsia, there is poor development of the placenta (the afterbirth) whereby the baby connects to the mothers blood supply for nutrients and oxygen. Drug that lead to improved development of the blood vessel connections between the mother and the baby and that result in better blood flow between the mother and baby may prevent or be used to treat pre-eclampsia. Much work has been done to demonstrate that carbon monoxide, a gas which at high concentrations is lethal, is an important substance at low concentrations that plays important roles in non-pregnant and pregnant humans. We propose to develop new approaches to increasing the normal production of carbon monoxide in humans as well as external exposure to low doses of carbon monoxide in pregnancy. The approaches will be used in placenta tissue and animal models as first steps in drug development towards the prevention and treatment of pre-eclampsia. We will carry out three approaches: 1. To determine if inhaled low amounts of carbon monoxide is effective and safe in mother and baby studies involving a pregnant mouse model of pre-eclampsia and in non-pregnant humans, 2. We will determine the effectiveness and safety of drugs that release carbon monoxide in pregnant mouse models of pre-eclampsia, and 3. We will determine the effect of drugs that increase the production of carbon monoxide in animals.