Nanomedicine Targeted Delivery Of Therapeutics To The Placenta To Treat Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$513,148.00
Summary
Preeclampsia, one of the most serious complications of pregnancy, affects around 3-8% of all pregnancies. Sadly, there is no treatment. We have developed a new technique to deliver treatments only to the placenta, sparing the mother and baby from side effects. We will test whether this technique can treat the source of preeclampsia, the placenta, in human and mouse models in our laboratory. This work has potential to offer possibilities of new treatments to other pregnancy complications.
Plasma Exchange And Glucocorticoids In Anti-neutrophil Cytoplasm Antibody Associated Systemic Vasculitis: A Randomised Controlled Trial (PEXIVAS Australia)
Funder
National Health and Medical Research Council
Funding Amount
$420,110.00
Summary
ANCA-associated vasculitis is a life-threatening disease. The PEXIVAS trial will investigate whether plasma exchange, in addition to immunosuppressive therapy and glucocorticoids, will reduce death and the development of severe kidney failure due to this disease. Additionally, the project will also look at whether using a reduced dose of glucocorticoids is just as effective as larger doses in lessening the infectious complications of treatment.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Prevention And Treatment Of Chronic Heart And Kidney Disease Via Epidemiological, Pharmacol Device And Cell-Based Approaches
Funder
National Health and Medical Research Council
Funding Amount
$5,795,334.00
Summary
Heart failure describes where the heart cannot pump adequately to meet the needs of the body. This condition has a high mortality despite recent advances in therapy, therefore, there is an urgent need for new approaches to this condition. The present grant aims to: (1) identify patients at high-risk for future development of this condition where early intervention with drugs may reduce or prevent the development of new heart failure; (2) use novel drugs, devices and stem cell therapies to identi ....Heart failure describes where the heart cannot pump adequately to meet the needs of the body. This condition has a high mortality despite recent advances in therapy, therefore, there is an urgent need for new approaches to this condition. The present grant aims to: (1) identify patients at high-risk for future development of this condition where early intervention with drugs may reduce or prevent the development of new heart failure; (2) use novel drugs, devices and stem cell therapies to identify ways to better treat patients with existing disease; (3) focus on the effect of heart failure on the kidney and vice versa via early diagnosis and treatment strategiesRead moreRead less
The Analgesic Evaluation Of Novel Natural Products From The Australian Plant Barringtonia Acutangula
Funder
National Health and Medical Research Council
Funding Amount
$174,500.00
Summary
This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that wi ....This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that will allow for their pharmacological evaluation as potential analgesic drugs.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
New Generation Antiplatelet Therapies To Prevent Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$483,148.00
Summary
Preeclampsia, a major complication of pregnancy, affects around 3-8% of pregnancies. Sadly, there is no way to prevent or delay disease. We have uncovered antiplatelet agents, used to prevent heart disease and stroke, may provide health benefits to women at risk of developing preeclampsia. We will test whether these agents can prevent the pathophysiology of preeclampsia in specialized human & mouse models developed in our laboratory. This work may provide a prevention strategy for preeclampsia.
Novel Approaches To The Prevention And Treatment Of Chronic Heart Disease And Its Co-morbid Complications
Funder
National Health and Medical Research Council
Funding Amount
$5,793,580.00
Summary
Cardiovascular disease (CVD) and its associated additional disorders constitute major public health problems, especially given the rapidly ageing population which is increasingly affected by obesity and diabetes. This Program will explore novel therapies for the treatment of CVD and associated diseases, particularly focussing on chronic kidney disease, translating preliminary laboratory-based findings into clinical trials and then clinical and epidemiological findings into practice and policy.
Plasma Exchange And Glucocorticoids In ANCA Associated Vasculitis: A Randomised Controlled Trial (PEXIVAS Australia)
Funder
National Health and Medical Research Council
Funding Amount
$635,243.00
Summary
Vasculitis is a life-threatening disease, and the current treatment for this condition is not satisfactory. This clinical trial aims to determine 1) if plasma exchange can lower mortality and the development of severe kidney failure due to this disease, and 2) if the use of lower doses of corticosteroids can lessen the infectious complications of treatment. This trial is part of a major international effort which will involve a total of 500 patients from Australia, UK, Europe, USA and NZ.
The Mutagenic Influence Of 5-methylcytosine And Its Relevance For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$844,462.00
Summary
Over time our cells accumulate damage to their DNA, which introduces mistakes in the genetic code. These mistakes can alter genes that regulate cell growth and survival and, in this way, they begin the process of turning a normal cell into a cancer. This research is investigating the cellular repair mechanisms that safeguard against DNA damage. Manipulating these repair mechanisms may offer a new way to treat cancer, by selectively inducing DNA damage within cancer cells.