According to current National Heart Foundation surveys high blood pressure affects almost 3 million Australians, and accounts for about 6% of the total burden of disease. Unless effectively treated, high blood pressure may result in serious complications such as stroke, heart attacks and heart failure. Despite the fact that there are now many effective blood pressure-lowering medications available, blood pressure control in the community is often poor. The cause of high blood pressure in most pe ....According to current National Heart Foundation surveys high blood pressure affects almost 3 million Australians, and accounts for about 6% of the total burden of disease. Unless effectively treated, high blood pressure may result in serious complications such as stroke, heart attacks and heart failure. Despite the fact that there are now many effective blood pressure-lowering medications available, blood pressure control in the community is often poor. The cause of high blood pressure in most people is unknown, but there is consistent information from population studies that low vitamin C intake is associated with high blood pressure. Recently, it has been shown that a diet rich in fruit and vegetables can lower blood pressure. We recently demonstrated in a small study that vitamin C tablets for one month lowered blood pressure, suggesting that vitamin C was the key beneficial element of the fruit and vegetable diet. Interestingly, some recent work suggests that the recommended daily allowances of vitamin C are less than a third of what they need to be to get effective levels of vitamin C in body tissues. Studies in animal models of high blood pressure have shown that oxidant levels are increased. This can affect the ability of blood vessels to relax, and may be a cause, rather than a result of high blood pressure. It seems possible that vitamin C (a strong antioxidant) may be having its beneficial effect by reducing 'oxidant stress' in blood and blood vessel walls. The purpose of this project is to further determine the effect of oxidants and antioxidants (specifically vitamin C) on blood pressure and blood vessel function in patients with high blood pressure. It is clearly prudent to eat a diet rich in fruit and vegetables, but it is important that we understand why this is so, and whether specific dietary components are critical. Vitamin C might potentially make a major impact on the presence and severity of high blood pressure in the Australian community.Read moreRead less
Angiotensin AT2 Receptor: A Novel Target For Cardiovascular Modulation
Funder
National Health and Medical Research Council
Funding Amount
$692,040.00
Summary
The hormone, angiotensin II, circulates in the blood and increases blood pressure and thickens the heart and blood vessels, all of which contributes to high blood pressure (hypertension). Angiotensin II causes these excitatory effects by acting at particular target sites called AT1 receptors. Drugs called AT1 receptor antagonists are known to block these excitatory actions of angiotensin II at AT1 receptors. Consequently, these compounds lower blood pressure in humans because they block the ongo ....The hormone, angiotensin II, circulates in the blood and increases blood pressure and thickens the heart and blood vessels, all of which contributes to high blood pressure (hypertension). Angiotensin II causes these excitatory effects by acting at particular target sites called AT1 receptors. Drugs called AT1 receptor antagonists are known to block these excitatory actions of angiotensin II at AT1 receptors. Consequently, these compounds lower blood pressure in humans because they block the ongoing stimulatory action of angiotensin II. However, it is now thought that angiotensin II may also be able to act at another target site (AT2 receptor) to cause opposite effects, i.e. decrease blood pressure and inhibit growth effects. Therefore, this project will examine if direct stimulation of AT2 sites can alter blood flows measured in different body regions in hypertensive rats as part of their mechanism to lower blood pressure. In addition, the effects of continuous stimulation of the AT2 site will be examined in hypertensive rats which will be implanted with a radiotransmitter to measure blood pressure without interference, and afterwards, structural measurements of the heart and blood vessels will be made. Additionally, this project will investigate whether stimulation of the AT2 site also contributes to the blood pressure-lowering effect of drugs already mentioned (AT1 receptor antagonists). The rationale for this is that the hormone angiotensin II is still 'free' to act at the AT2 site, even with AT1 receptors being blocked, and lower blood pressure. These studies will determine if stimulation of AT2 sites contributes to the beneficial effects (i.e. decreased blood pressure and decreased cardiovascular growth) of AT1 receptor antagonists in the treatment of high blood pressure. More importantly, these findings may also identify a new therapeutic target site (AT2 receptor) for drug development in the treatment of cardiovascular disease.Read moreRead less
Next-generation Glioblastoma Multiforme Therapies Based On Multistage Delivery Nanovectors
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Nanomedicine provides novel therapies with enhanced treatment success and reduced side effects, which improve the patient’s quality of life. Drug delivery systems that are able to treat highly drug-resistant tumours such as glioblastoma multiforme (GBM) are a key target for nanomedicine-based therapies. We will investigate a new GBM treatment by developing a multistage delivery nanovector to selectively carry and release a combination of chemical and physical therapeutics.
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.
Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.
Antibiotic Potentiators As An Alternative Therapeutic Option For The Treatment Of Extensively Drug-resistant Gram-negative Infections
Funder
National Health and Medical Research Council
Funding Amount
$856,858.00
Summary
Antibiotic mono-therapies are increasingly ineffective for hard-to-treat bacterial infections, forcing clinicians to rely on combinations of antibiotics. Our project has identified compounds that have weak to no antimicrobial potency in their own right, yet when combined with an existing antibiotic they potentiate its activity and restore its ability to treat resistant infections. These antibiotic potentiators are exciting alternatives to current therapies with reduced risk of induced resistance
Treatments that target cancer causing genes called oncogenes have resulted in new treatment paradigms for cancer. We suggest that outcomes of patients with cancer will be further substantially improved by understanding how cancers can overcome resistance to these treatments that develops in many patients. To accelerate the adoption of these and other new treatments for cancer we will also develop new frameworks for clinical trials.
There is an unmet medical need to develop new therapies that are safer and potentially allow the treatment of a broader range of cancers. Inhibiting the immune checkpoints TIGIT and CD96 represents an opportunity that may parallel and indeed complement the activity and impact of other lymphocyte checkpoint inhibitors in human cancer (eg. PD1/PD-L1). While testing these as targets in mice we will also learn more about their ligand CD155 and their expression in human tumors.
Effectiveness Of Training Somatosensation In The Hand After Stroke: A Randomized Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$180,660.00
Summary
Stroke is a leading cause of death and disability, requiring provision of rehabilitation services to help minimize impairment and its impact on the ability to resume daily activities. The ability to feel textures and objects through touch and to know where one s limbs are in space are impaired in up to 85% of people who have suffered a stroke. People with this loss are handicapped by difficulties in exploring objects through touch and in performing everyday tasks that require grasp and manipulat ....Stroke is a leading cause of death and disability, requiring provision of rehabilitation services to help minimize impairment and its impact on the ability to resume daily activities. The ability to feel textures and objects through touch and to know where one s limbs are in space are impaired in up to 85% of people who have suffered a stroke. People with this loss are handicapped by difficulties in exploring objects through touch and in performing everyday tasks that require grasp and manipulation of objects. Yet clinicians are either not treating the problem or are using methods without a sound theoretical basis and controlled evidence to support their application. We have systematically investigated optimal methods of sensory training across different sensory abilities using a series of single-subject experiments. Marked improvement in the ability to discriminate trained and related untrained texture stimuli and limb positions was achieved and maintained in most participants. These findings have provided the foundation for development a scientifically based and clinically focused sensory retraining program that has apparently excellent therapeutic potential. The purpose of the proposed study is to test the effectiveness of this scientifically based, clinical sensory retraining program in a broad group of stroke clients using the internationally recommended randomized controlled group design. The program will train a range of functionally important sensory discrimination tasks, i.e. texture discrimination, limb position sense and tactual object recognition, in clinical and home environments. Demonstration of clinically important and statistically significant training effects will provide the evidence necessary to recommend the introduction of the program into routine health service delivery. Investigation of patient characteristics that may impact on the ability to benefit from training will assist in the targeting of services to appropriate individuals.Read moreRead less
Engineered Cell And Exosome Therapy For Pulmonary Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$838,490.00
Summary
Diseases affecting the blood vessels in the lungs cause early death and the currently available treatments are not curative. We will take advantage of the latest developments in the understanding of the molecular basis of these diseases to design and test a new treatment approach using cells and cell-derived products as a therapy.