Triple Therapy Prevention Of Recurrent Intracerebral Disease EveNts Trial (TRIDENT)
Funder
National Health and Medical Research Council
Funding Amount
$5,256,292.00
Summary
Acute intracerebral haemorrhage (ICH) is a serious form of stroke. Survivors of ICH are at high risk of repeat events. Blood pressure lowering is a very important to prevent repeat events but data shows blood pressure is poorly controlled in these patients. In this research we investigate whether an approach that uses a 'triple pill' strategy (3 low dose BP drugs in one pill) in ICH patients with mild to moderate hypertension can decrease major cardiovascular events.
Contribution Of Ovarian Cancer Stem Cells To Chemoresistance And Recurrent Disease.
Funder
National Health and Medical Research Council
Funding Amount
$378,940.00
Summary
Ovarian cancer is the most lethal gynaecological cancer. Previously, we showed that cancer stem cells are the “beating heart” of the ovarian cancer and are responsible for drug resistance and tumour relapse. The ineffective targeting of these cells by chemotherapy is accountable for the poor clinical outcomes in ovarian cancer patients. This project will define the molecular signals involved in maintenance of cancer stem cells and develop targeted therapies against these cells.
Antiphospholipid Antibodies, Beta 2-Glycoprotein I And Control Of Coagulation.
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in ....Antiphospholipid antibodies are associated with an autoimmune condition characterised by the presence of clots and recurrent miscarriages. Although the name implies that the antibodies bind phospholipid the disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2-Glycoprotein I. The exact role of Beta 2-GPI in the body has not been determined, although there are numerous studies looking at this protein. This protein has been thought to be important in controlling the clotting system in humans and other mammals. The evidence for this has been contradictory, however, we have recently made a major new finding on the function of this protein on the clotting system. We will be using sophisticated molecular biology techniques to further characterise the role that Beta 2-GPI has in controlling clotting factors in the body. We have been able to eliminate the gene for Beta 2-GPI in mice thus deriving mice that do not produce any Beta 2-GPI protein. These mice are called Beta 2-GPI knockout mice and will be an ideal animal model to examine the function of Beta 2-GPI and its new role in controlling the clotting cascade by targetting a specific part of this pathway. In addition, these findings may be able to provide new information on how Beta 2-GPI controls clotting factors and the effect of antiphospholipid antibodies on this system, which may lead to new treatments for antiphospholipid antibodies and more generally clotting disorders.Read moreRead less
Characterisation Of An In-vivo Thrombosis Animal Model Of The Antiphospholipid Syndrome Using Beta 2-GPI KO Mice
Funder
National Health and Medical Research Council
Funding Amount
$467,310.00
Summary
The antiphospholipid syndrome is an autoimmune condition characterised by the presence of thrombosis and recurrent miscarriage. The disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2- Glycoprotein I. This protein has been thought to be important in controlling the clotting system in humans and other mammals. However, the experiments that have been designed to look at the function of this protein have looked at its function in the test tube. The ....The antiphospholipid syndrome is an autoimmune condition characterised by the presence of thrombosis and recurrent miscarriage. The disorder is characterised by circulating antibodies which bind a protein in the blood known as Beta 2- Glycoprotein I. This protein has been thought to be important in controlling the clotting system in humans and other mammals. However, the experiments that have been designed to look at the function of this protein have looked at its function in the test tube. The exact role of Beta 2-GPI in the body, has not been determined. A way of looking at the function of this protein in the body would be if you eliminated the protein from an animal such as a mouse. By sophisticated molecular biology techniques we have been able to eliminate the gene for Beta 2-GPI in mice thus deriving mice that do not produce any Beta 2-GPI protein. These mice are called Beta 2-GPI knockout mice and are an ideal animal model to examine the function of Beta 2-GPI. Experiments outlined in this proposal will examine the role of Beta 2-GPI in clotting, atherosclerosis and the effect of production of antibodies to Beta 2-GPI in these animals. In addition, since current treatment of patients that have these antibodies consists of long term, sometimes lifelong, treatment with drugs that thin the blood which have potential side effects, we are investigating a novel treatment approach which is directed at eliminating the antibodies that bind Beta 2-GPI. If one could eliminate the antibody production to Beta 2-GPI by these patients there would not be a need for lifelong treatment with drugs such as heparin which thins the blood and there would thus be a reduction in the problems with these medications. To do this we have obtained a specialised chemically modified portion of Beta 2-GPI that has already been shown to work in preliminary experiments.Read moreRead less
This study aims to determine the extent to which semen is important in initiating the maternal immune response to the fetus and placenta during pregnancy. We postulate that exposure to paternal proteins in sperm and other factors present in the semen may have a cumulative, beneficial effect in 'educating' the female immune system to respond in the correct way to the embryo when pregnancy occurs. To investigate this, the behaviour and movements of white blood cells responding to semen will be stu ....This study aims to determine the extent to which semen is important in initiating the maternal immune response to the fetus and placenta during pregnancy. We postulate that exposure to paternal proteins in sperm and other factors present in the semen may have a cumulative, beneficial effect in 'educating' the female immune system to respond in the correct way to the embryo when pregnancy occurs. To investigate this, the behaviour and movements of white blood cells responding to semen will be studied during the period after mating, in which the uterus prepares for and accommodates to pregnancy. In particular, the study will focus on the roles of a specific chemical messenger substance in semen, called transforming growth factor (TGF)-beta, which triggers the molecular changes leading to maternal immune tolerance. A deeper understanding of these events will have an important impact in human and veterinary medicine where implantation failure is a major cause of reproductive loss and inadequate placental growth poses a threat to the health of the conceptus both in utero and into adult life.Read moreRead less
Pathophysiological Mechanisms In The Antiphospholipid Syndrome: B2GPI Regulation Of FXI-FXIa
Funder
National Health and Medical Research Council
Funding Amount
$530,591.00
Summary
The major protein that the antibodies in the antiphospholipid syndrome (APS) bind is called Beta 2-GPI. Antibodies to Beta 2-GPI are associated with recurrent miscarriage, intrauterine growth retardation, clots and stroke. Treatment of patients with the APS are treated with medication that has significant side effects. The development of more targeted and effective therapies for the APS requires a greater understanding of how the antibodies cause their effects, which is addressed in this study.
IMPROVING STROKE OUTCOMES: NEW TARGETS AND THERAPIES
Funder
National Health and Medical Research Council
Funding Amount
$7,212,064.00
Summary
Previously we established a unique collaboration of researchers from the basic and clinical sciences.. The main aim of this ' vertically integrated ' model was to develop new therapies to improve stroke outcomes. We developed a system to identify ' off-the-shelf ' compounds which protect the brain after stroke onset. This involves data assimilation (meta-analysis) in a unique way, an approach which has attracted attention internationally. We are also completing an important clinical trial using ....Previously we established a unique collaboration of researchers from the basic and clinical sciences.. The main aim of this ' vertically integrated ' model was to develop new therapies to improve stroke outcomes. We developed a system to identify ' off-the-shelf ' compounds which protect the brain after stroke onset. This involves data assimilation (meta-analysis) in a unique way, an approach which has attracted attention internationally. We are also completing an important clinical trial using the clot dissolving agent tPA to extend the time during which the drug may be effective beyond the three-hours currently used. In the next phase of our program we plan to expand the basic science component to identify parts of brain cells (axons and dendrites) which may yield important information about new drugs to protect the brain. We will use our novel summary data technique to test drugs in animal models more appropriate to the human stroke paradigm than have been used in the past In clinical studies we will follow our theme of identifying new targets for therapy using sophisticated PET and MRI imaging techniques, both in patients who are at great risk of stroke recurrence after a minor warning stroke and those with stroke caused by bleeding within the brain. These studies will provide information about predictors of recurrent and worsening stroke which may be modified by new therapies. The final stage in identifying new therapies is the Phase III clinical trial. We will complete one of these in which the most appropriate drug preventing further strokes in a major new stroke subtype will be identified. Toward the end of the program, we will commence phase 3 studies of drugs we have selected as being most likely to protect the brain based on our animal experiments. The main benefit of this unique collaborative research model is to efficiently identify new therapies to reduce the burden of stroke, currently the second most common cause of death globally.Read moreRead less
Shared Team Approach Between Nurses And Doctors For Improved Risk Factor Management (STAND FIRM)
Funder
National Health and Medical Research Council
Funding Amount
$1,945,676.00
Summary
There are many proven treatments for preventing people with stroke from having a recurrent event, e.g. maintaining blood pressure at acceptable levels. However, uptake of therapies is poor. We will assess whether patients receiving individualised management plans, prepared and administered by both doctors and nurses will have risk factors controlled better than those receiving usual care. The plan includes education of patients to help them have more control over their own care.