Targeting The Anti-angiogenic Factors Of Preeclampsia: Soluble Endoglin And SFlt1
Funder
National Health and Medical Research Council
Funding Amount
$447,024.00
Summary
Preeclampsia is a severe disease of pregnancy - the placenta releases toxins in to mum's bloodstream that circulate her body and damage her organs. As there are no efficacious treatments, clinicians are forced to deliver babies irrespective of gestation. Although the two toxins of preeclampsia have been identified, little is known about their regulation. This project aims to elucidate the regulation of these toxins and design therapeutics that can prevent their release in the clinic.
Understanding The Myometrial Transition At Term And Preterm Labour To Guide Tocolysis
Funder
National Health and Medical Research Council
Funding Amount
$808,447.00
Summary
This grant seeks to understand how the muscle cells of the uterus transform at the time of labour. We propose that this transformation is organised by enzymes that modify the histones around key genes. We will test if a similar pathway operates in cases of preterm labour. The results will guide the development of new ways of treating premature labour that will use targeted nanoparticles to deliver siRNA directly to the muscle cells of the uterus.
Soluble Endoglin In The Pathogenesis Of Preeclampsia: Investigation Of Mechanisms And The Development Of Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$572,733.00
Summary
Preeclampsia is a severe disease of pregnancy. As the pathogenesis is poorly understood, the only treatment is for clinicians to deliver babies irrespective of gestation. We have identified MMP-14 as the molecular scissors that release soluble endoglin from placenta, a toxin centrally responsible for severe preeclampsia. In this project we aim to further investigate the mechanisms governing soluble endoglin release and to begin developing a potential therapeutic for use in the clinic.
Developing Diagnostics And Therapeutics For Preeclampsia: Targeting A Novel Placental Specific SFlt-1 Variant
Funder
National Health and Medical Research Council
Funding Amount
$722,283.00
Summary
Preeclampsia is a dreaded disease of pregnancy, globally responsible for thousands of deaths of mothers and babies. It is caused by a protein called sFlt-1 leaking out of the placenta and attacking the mothers organs. Recently, a new sflt-1 subtype was discovered that is specific to the placenta. It may be the key disease causing toxin in preeclampsia. We will target this placental specific sFlt-1 to generate diagnostics to predict preeclampsia, and explore novel ways to block the toxic effects ....Preeclampsia is a dreaded disease of pregnancy, globally responsible for thousands of deaths of mothers and babies. It is caused by a protein called sFlt-1 leaking out of the placenta and attacking the mothers organs. Recently, a new sflt-1 subtype was discovered that is specific to the placenta. It may be the key disease causing toxin in preeclampsia. We will target this placental specific sFlt-1 to generate diagnostics to predict preeclampsia, and explore novel ways to block the toxic effects of sFlt-1 as a strategy to develop drugs.Read moreRead less
Systematic Screening Approach To Identify New Therapeutics For Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$727,529.00
Summary
Preeclampsia is a pregnancy complication where factors are released from the placenta into the mum's bloodstream, causing widespread blood vessel and organ damage. Sadly, there is no treatment. Our laboratory has a set up a system to test whether drugs might be useful as a treatment for preeclampsia. We test whether the drugs decrease the release of these factors and protect blood vessels. In this grant, we propose testing three exciting drug treatments for preeclampsia.
Multicentre Trial Of Calcium Channel Blocker Versus Calcium Channel Blocker Plus Cox2 Inhibitor In Preterm Labour
Funder
National Health and Medical Research Council
Funding Amount
$644,130.00
Summary
Preterm birth is a major problem in our society, and has enormous consequences for parents and children. It also has a major impact on scarce financial resources. When women present in preterm labor, current therapies have only limited success in stopping contractions and postponing birth. They have not been shown to reduce the rates of the serious neonatal problems associated with prematurity. This project will be coordinated in Newcastle, N.S.W., and will involve major perinatal centres throug ....Preterm birth is a major problem in our society, and has enormous consequences for parents and children. It also has a major impact on scarce financial resources. When women present in preterm labor, current therapies have only limited success in stopping contractions and postponing birth. They have not been shown to reduce the rates of the serious neonatal problems associated with prematurity. This project will be coordinated in Newcastle, N.S.W., and will involve major perinatal centres throughout Australia, along with overseas centres. It will test a new combination of drugs for their ability to postpone delivery in women presenting with preterm labour. It is postulated that the combination of drugs will be more effective than existing therapies. The drugs used in the trial are Nifedipine and Rofecoxib. Complications of prematurity include neonatal death, cerebral palsy, visual and hearing impairment, and chronic lung disease. These complications are most significant in extremely premature infants - in particular, those under 28 weeks gestation at the time of their delivery. For this reason, the study will focus only on women presenting in labour below 28 weeks. The ability to stop labour is important, but the main aim of any treatment for preterm labour is to reduce the rates of neonatal death and handicap. Babies born to women enrolled in this study will be followed for a period of one year after birth to assess their outcomes. It is our hypothesis that the combination of Rofecoxib and Nifedipine will result in lower rates of death and handicap in babies than Nifedipine alone. In addition, we will examine the rates of side effects in women receiving therapy. Currently used therapies, including intravenous ventolin, have high rates of maternal side effects. Nifedipine and Rofecoxib have both been shown to have low rates of maternal side effects.Read moreRead less
Defining the pathways of developmental brain injury, for a healthy start to life. Injury to the developing brain, whether sustained during pregnancy or at birth, is the underlying cause of many cognitive and motor disabilities, including cerebral palsy. This project will identify the cellular pathways that cause developmental brain injury, arising from the three principal complications of pregnancy or birth; intrauterine growth restriction (IUGR), preterm birth with/without intrauterine infectio ....Defining the pathways of developmental brain injury, for a healthy start to life. Injury to the developing brain, whether sustained during pregnancy or at birth, is the underlying cause of many cognitive and motor disabilities, including cerebral palsy. This project will identify the cellular pathways that cause developmental brain injury, arising from the three principal complications of pregnancy or birth; intrauterine growth restriction (IUGR), preterm birth with/without intrauterine infection and birth asphyxia. This project will utilise this knowledge of the causal pathways leading to brain injury to implement targeted therapies to reduce injury or repair the brain. It will progress fundamental biomedical discoveries into clinical practice to decrease the incidence and severity of newborn brain injury and cerebral palsy.Read moreRead less