Preclinical Evaluation Of A Novel Allosteric IL-1R Inhibitor (rytvela) For The Prevention Of Perinatal Inflammation-induced Fetal Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,377,827.00
Summary
Interleukin-1 (IL-1) is a potent inflammatory protein involved in many inflammatory disorders, including preterm birth (PTB). Blocking the actions of IL-1 in pregnancies at risk of delivering preterm may protect the fetus from PTB and the long-term harm of exposure to inflammation before birth. Using four different models of antenatal inflammation, we will explore the use of a new IL-1 inhibitor to see if it blocks inflammation ‘in utero’ and improve neonatal health and development.
The Immune Modulatory Function Of Chondroitin Sulphate A In Placental Malaria: Protecting The Fetus, Promoting The Parasite?
Funder
National Health and Medical Research Council
Funding Amount
$529,206.00
Summary
Pregnant women and their babies are susceptible to placental malaria infection. Malaria parasites infect the placenta by binding to chondroitin sulfate A (CSA). CSA levels increase in normal pregnancy. Studies suggest that CSA can suppress immune cell function. This study will look at the immune modulating function of CSA during pregnancy and placental malaria. CSA may act as camouflage, hiding the malaria parasite from immune cells. This may be a novel immune evasion pathway.
Fetal Sex: An Important Determinant Of The Placental Transcriptome
Funder
National Health and Medical Research Council
Funding Amount
$553,574.00
Summary
There are fetal sex differences in pregnancy outcomes that place boys at greater risk than girls. These are likely caused by genetic differences in the placenta. We will use 21st century gene sequencing technology to obtain the complete sequence of placental genes in early pregnancy and normal term placenta to determine what the genetic differences are between male and female placentas. This may be important in developing future sex specific therapeutics for babies in the neonatal nursery.
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
Is Placental Aging The Key To Understanding, Predicting And Preventing Stillbirth?
Funder
National Health and Medical Research Council
Funding Amount
$473,861.00
Summary
Stillbirth occurs in 35 times as many pregnancies as sudden infant death but the causes are unknown. This project will help to develop tests that can predict the risk of stillbirth so that the obstetrician can deliver the baby before it dies. The investigators hypothesise that stillbirth is due to aging of the placenta and that markers of the aging placenta can be detected in the mother’s blood. The project brings together experts in the placenta, aging and obstetric care of high risk pregnancy.
This project will substantially improve our understanding of the potential causes of vascular complications of pregnancy including preeclampsia, and provide a solid foundation to develop new clinical interventions for women who develop this disease during their pregnancy. It will also investigate if a peptide hormone, relaxin, could be an effective treatment to manage the health of women diagnosed with preeclampsia during their pregnancy and prevent delivery of severely premature infants.
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.
The Role Of Vitamin D In Placental Development And Pregnancy Success
Funder
National Health and Medical Research Council
Funding Amount
$723,235.00
Summary
Vitamin D deficiency affects about 1 billion people worldwide, including up to 80% of Australians depending on age, skin colour and sun exposure. Vitamin D deficiency has now been associated with a large number of common diseases of aging and with pregnancy complications. This proposal will use human pregnancy serum and placenta, as well as mouse gene knockout models, to determine the hitherto unknown roles of vitamin D in development of the placenta and health of mother and baby.
Priming The Maternal Immune Response To Resist Inflammatory Disorders Of Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$920,972.00
Summary
Preeclampsia and preterm birth are common conditions affecting >15 million pregnancies annually. An underlying cause is the mother’s immune response, which can react adversely to the fetus causing an inflammatory reaction. This project seeks to find ways to strengthen the maternal immune system beginning before conception. The work will provide insights upon which to advise intending parents and will inform development of new treatments options to protect susceptible women.
The placenta is essential for fetal-maternal exchange and healthy pregnancy however the factors that are required for the placenta to form are poorly understood. We will investigate how the placenta develops in mice and which are the most important factors that are required for a health placenta to form.