Investigating The Impact Of Coincident Modulation Of Adenosine And Glutamate Receptors On Neuronal Activity – Implications For CNS Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Dementia in particular Alzheimer's disease, is one of the leading causes of death. There remains a need for new drugs to treat both symptoms and disease progression. Two receptors in the brain, the adenosine A1 (A1AR) and metabotropic glutamate 5 (mGlu5) are suggested to be promising new drug targets for dementia. In order to better develop drugs that target these receptors, we will develop a better understanding of activity of these receptors under conditions of health and disease.
Adenosine Receptor Antagonists As Immunotherapeutic Agents For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$555,779.00
Summary
We have shown that drugs that block immunosuppressive adenosine receptors can improve anti-tumour immune responses and consequently enhance the effectiveness of chemotherapy. These drugs are already known to be well-tolerated in humans and so have great potential for clinical development. We propose to determine the therapeutic response achieved with these drugs in combination with established cancer treatments involving radiotherapy and immune based therapies.
Targeting Adenosine Mediated Immunosuppression To Enhance CAR T Cell Activity
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
The use of white blood cells genetically engineered to eradicate cancer cells specifically has been a major breakthrough in cancer treatment. These cells (CAR T cells) are very effective in blood cancers, but do not currently work well in other cancers. This is due to the immune suppressing nature of the cancer environment. I propose to use strategies to overcome this by genetically reprogramming the CAR T cells to be resistant to suppression by the cancer and therefore be more effective.
The Role Of CD73 In Cancer: Validating A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
We here propose to investigate the role of a specific immune-suppressive molecule called CD73 in cancer. We will test the therapeutic activity of blocking CD73 with a monoclonal antibody for cancer treatment, either used alone or in combination with immune-activating agents and chemotherapy.
Co-inhibition Of Adenosine Generation And Signalling: A New Combination Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$587,857.00
Summary
Cancer is a major killer of Australians and there is a need to develop new combination therapies that halt cancer growth and spread. A metabolic product of the cancer called adenosine can be exploited by several different treatment approaches. Surprisingly we have found that both preventing adenosine generation and its effects on immune cells can together more effectively slow tumour growth and spread. If we can better understand why, this approach can be quickly brought it to clinical practice.
Adenosine Receptor Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$682,163.00
Summary
Adenosine A1 receptor (A1R) activation confers powerful protection to heart cells, however clinical application remains suboptimal due to adverse effects such as a slowing in heart rate and decrease in blood pressure. Importantly a new class of compounds, A1R biased agonists, can mediate potent cardioprotection in the absence of adverse effects. This proposal will establish the molecular mechanisms involved and the scope to develop A1R biased agonists as a novel approach to treat heart disease.
Adenosine Receptor Context-Specific Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,021,744.00
Summary
Heart attacks and secondary heart failure remain significant health burdens. Stimulation of adenosine receptors located on heart cells confers powerful cardiac protection, improving acute and longer-term heart function subsequent to a heart attack but avoiding the usual unwanted effects from this approach. We aim to better understand the mechanism of action of potential adenosine receptor therapeutics and establish the clinical potential of these compounds using animal models of heart failure.
Understanding Mechanisms Of Allostery And Biased Agonism At The Adenosine A1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$603,033.00
Summary
This project focuses on an important protein found in the heart. Drugs that activate this protein can protect the heart against damage that occurs after a heart attack, but they all have undesirable side effects. We have discovered a new class of molecule that can protect the heart without these side effects. We now seek to understand how these compounds work at the molecular level. This knowledge can facilitate the design of safer medicines for the treatment of cardiovascular disease.
Mechanisms Of A Novel Strategy For Neuroprotection In Experimental Models Of Stroke And Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$480,499.00
Summary
Stroke and epilepsy are among the most common neurological disorders affecting many Australians. In both disorders, brain metabolism is disturbed. Dr. Borges has found that an edible oil inhibits seizures in mice and it is now being tested in epilepsy patients. This grant will allow her laboratory to study the effects of this oil against stroke and to investigate how it protects the brain. New knowledge obtained will help to develop new treatments for brain disorders.
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.