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The Role Of PI 3-kinase P110beta In Regulating Thrombus Porosity
Funder
National Health and Medical Research Council
Funding Amount
$518,394.00
Summary
Blood clots blocking blood flow to the brain (stroke) are a major cause of death and disability. Safety concerns limit the use of current therapies to a small subset of patients, and there is an urgent need to identify safer, more effective drugs. Our studies show that inhibitors of the enzyme PI3Kbeta increase the breakdown of blood clots, without increasing bleeding risk. Our preliminary results raise the possibility that PI3Kbeta inhibitors may represent a safe and effective new approach for ....Blood clots blocking blood flow to the brain (stroke) are a major cause of death and disability. Safety concerns limit the use of current therapies to a small subset of patients, and there is an urgent need to identify safer, more effective drugs. Our studies show that inhibitors of the enzyme PI3Kbeta increase the breakdown of blood clots, without increasing bleeding risk. Our preliminary results raise the possibility that PI3Kbeta inhibitors may represent a safe and effective new approach for the treatment of stroke.Read moreRead less
Talk Stroke: Developing Australia's First National Tele Stroke Framework And Communications Platform
Funder
National Health and Medical Research Council
Funding Amount
$1,164,847.00
Summary
Patients with a stroke in the regional areas are twice as likely to suffer significant disability compared to patients living in inner city regions. We propose to develop technology to close this gap, and guide its implementation with a national tele stroke policy framework. The technology we develop with our partner organisations will facilitate tele medicine to close the gaps in critical patient care.
Helping Stroke Physicians Choose Who To Thrombolyse - The Targeting Optimal Thrombolysis Outcomes (TOTO) Study
Funder
National Health and Medical Research Council
Funding Amount
$1,073,140.00
Summary
Thrombolysis using alteplase is one of the most effective treatments for stroke but is currently used in only 5% of stroke cases. A major barrier is a lack of tools to identify who will benefit from treatment, or who might have a major adverse event. In this study we will develop a clinical decision rule based on clinical data, advanced CT imaging, and blood biomarkers to help identify those who will benefit and those likely to bleed, to encourage wider use of this treatment in acute stroke.
Restoring Microcirculatory Perfusion In ST-elevation Myocardial Infarction: The RESTORE MI Study
Funder
National Health and Medical Research Council
Funding Amount
$3,274,537.00
Summary
Current heart attack treatments have focussed on re-opening the blocked coronary artery but despite this, many patients still suffer significant heart damage because of inadequate blood flow to the heart muscle due to damage to the small blood vessels - the microcirculation. This study seeks to identify heart attack patients with damage to the microcirculation and will conduct a randomised trial of clot busting medications to reduce microcirculation damage and to improve heart function.
Characterising The Role Of Streptokinase Polymorphism In Invasive Pathogenesis Of Streptococcus Pyogenes.
Funder
National Health and Medical Research Council
Funding Amount
$480,535.00
Summary
Invasive bacterial pathogens such as Streptococcus pyogenes, can hijack host proteins and use them to facilitate the disease process. S. pyogenes secrete streptokinase to activate a host protease (plasminogen) which is used by the bacterium to invade through host tissue. This project will characterise the molecular mechanisms involved in streptokinase mediated activation of plasminogen which will assist the generation of novel therapeutics to treat invasive diseases.
Thrombolysis is a method of dissolving the blood clot that is the cause of the majority of strokes in Australia. The first major trial to demonstrate benefit for this treatment was published some 11 years ago but treatment has not been widely implemented across Australia because of the difficulties in giving treatment within the very tight time window for which treatment is currently approved (patients must get to hospital, be scanned and start treatment within 3 hours of the onset of the stroke ....Thrombolysis is a method of dissolving the blood clot that is the cause of the majority of strokes in Australia. The first major trial to demonstrate benefit for this treatment was published some 11 years ago but treatment has not been widely implemented across Australia because of the difficulties in giving treatment within the very tight time window for which treatment is currently approved (patients must get to hospital, be scanned and start treatment within 3 hours of the onset of the stroke). Other factors which have limited implementation of treatment in Australia are continued debate over the trial data for this treatment as only one of the 5 major trials was positive. In addition, virtually no patients aged over 80 years old were included in the previous trials, and as this age group represents about a third of all stroke in Australia, new data in this age group is required. As a result of the difficulty in giving a treatment within such a tight time window and the ongoing debate about the trial data, few Australians are currently treated and thus the public health impact is negligible. In to change clinical practice, we need reliable data from a large convincing further trial of thrombolysis with the more realistic time window of 6 hours. The Third International Stroke Trial (IST-3) is a large international collaborative effort to determine whether thrombolysis treatment offered to a wider range of patients up to 6 hours from stroke onset results in an increase in long-term independent survival. Data from such a trial is most likely to change clinical practice and lead to an important public health benefit.Read moreRead less
Degradable Nanocapsules For Thromboprophylaxis And Treatment Of Acute Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$1,158,447.00
Summary
The consequences of fat build up in vessels such as heart attacks and brain infarcts are the major cause of death in Australia. Clot busters have been proven to be beneficial for patients with heart attacks, clots in the legs or lungs and brain infarcts. However, the currently available drugs have major limitations in efficacy and in safety. The aim of this project is to develop novel drugs that have the potential to improve both significantly.
Investigation Of A New Approach To Regulate Fibrin Clot Retraction And Arterial Thrombolysis
Funder
National Health and Medical Research Council
Funding Amount
$483,171.00
Summary
Pathological blood clots are removed in patients by administering clot dissolving drugs (fibrinolytics). However these drugs are quite often ineffective and cause bleeding. We have identified a new platelet-mediated pathway controlling contraction of blood clots, important for clot stability. In this proposal, we will examine the potential for inhibitors of this pathway to loosen blood clots, and facilitate the actions of fibrinolytics to promote clot dissolution.
Enhanced Control Of Hypertension And Thrombolysis In Stroke Study (STAY ENCHANTED)
Funder
National Health and Medical Research Council
Funding Amount
$2,437,384.00
Summary
"Clot busting" treatment is the only approved medical treatment for the commonest type of stroke, ischaemic stroke. However, uptake of treatment remains poor, mainly due to the known major risk of bleeding in the brain. STAY ENCHANTED is an international clinical trial to investigate whether "clot-busting" can be made safer using a lower dose and/or immediate blood pressure lowering. A safer more effective regime could have a major global health impact.
To Determine The Role And Mechanism Of Action Of Tissue-type Plasminogen Activator In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Tissue-type plasminogen activator (t-PA) is used clinically to remove blood clots. Recently, a role for t-PA in the brain was discovered where under pathological conditions it can promote ischaemic and excitotoxic brain injury. This project will examine the mechanisms by which t-PA promotes injury to brain cells. It is anticipated that results obtained could be used to devise a means to reduce t-PA toxicity in the brain that would be of therapeutic benefit for patients with ischaemic stroke.