The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
Contribution Of Complement C5a To Neuronal Cell Death During Ischemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$455,263.00
Summary
Ischemic stroke remains the second leading cause of death in Australia. This project aims to understand the role the innate immune system plays in neuronal cell death following ischemic stroke. We will use cellular and animal models of ischemic stroke, as well as examine patients affected by stroke, to explore and inhibit potential damaging immune factors generated by stroke tissue. By exploring these immune pathways, we aim to identify novel therapeutic targets to treat ischemic stroke.
Therapeutic Targeting Of Complement C5a Receptors In HuntingtonÍs Disease
Funder
National Health and Medical Research Council
Funding Amount
$468,312.00
Summary
HuntingtonÍs disease is a genetic neurodegenerative condition leading to progressive cognitive and motor deficits and eventual death. This research aims to explore the role of immune and inflammatory pathways in the progression of disease in patients suffering HuntingtonÍs disease, as well as in an animal model of this condition. By exploring these immune and inflammatory pathways, we aim to identify novel therapeutic targets to treat HuntingtonÍs disease.
Complement Activation As A Therapeutic Target And Clinical Biomarker For Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$497,941.00
Summary
Parkinson’s disease is the second most common neurological disease in Australia, yet there is no treatment to slow disease progression. Our study is investigating inflammation within the brain as a major contributing factor in Parkinson’s disease. We will examine this inflammatory pathway in human patients suffering from Parkinson’s, and will test a novel anti-inflammatory drug in animal models of Parkinson’s disease, in order to identify a novel treatment to reduce disease pathology.
Determining The Contribution Of Peripheral Immune Complement Signalling In The Progression Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,000,871.00
Summary
Motor neuron disease (MND) is a debilitating and lethal neurodegenerative disease, which has no effective treatment. We propose that an overactive immune system is a major contributing factor in this disease. To test this, we will examine immune pathways in patients suffering from MND, and will test a novel immune-modulatory drug in animal models of MND. We hope to identify new therapeutic avenues to slow disease progression, and improve the quality of life in patients diagnosed with MND.
Potent Small Molecule Modulators Of A Complement Protein In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$689,428.00
Summary
We have invented powerful new compounds that act on the cell surface and regulate inflammation. We plan to (1) fine-tune our small molecules for optimal activity on different kinds of immune cells; (2) understand mechanisms by which the compounds affect cellular inflammatory responses; (3) evaluate the compounds as potential treatments in rodent models of inflammatory diseases implicated from cell studies. This study is anticipated to lead to clinical studies for a new kind of drug treatment.
Downsizing A Human Protein To Modulate Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$516,793.00
Summary
We have discovered how to downsize a human protein to very small molecules with the same activities and potencies. Small changes enable the compounds to powerfully block the actions of the protein. These small molecules are very stable in blood, whereas the protein deactivates in minutes. This project will develop the small molecules into experimental drugs and test them in human cells and proteins, and in rats to evaluate their potential for treating human inflammatory diseases.
Novel Approaches To Control Mast Cell Function In Allergic Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$723,447.00
Summary
Allergic disorders are a major health problem. Driven by mast cells, the underlying inflammation is exacerbated by the ‘?c family’ of cytokines acting on the surface of these cells. We aim to characterise the ‘mast cell-?c axis’ with the view to developing new therapies based on our ?c receptors blocking antibodies. This path of discovery-mechanism-translation seeks to recapitulate our previous success of taking a related antibody to Phase II clinical trials to treat patients with leukaemia.
Targeting The Complement Cascade: A Novel Therapeutic Strategy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$546,496.00
Summary
The incidence of melanoma is increasing world-wide, and Queensland has the highest rate of melanoma in the world. Despite advances in treatment, the 3-year survival rate for metastatic melanoma remains extremely low. This project builds on our recent research demonstrating a role for a key component of the innate immune system (complement C3a) in melanoma growth. Specifically we seek to investigate the potential of C3a as a therapeutic target for metastatic melanoma.
Complement Inhibitors For Treatment Of Chronic Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$623,606.00
Summary
We aim to provide new therapeutic approaches to gum disease, which not only causes tooth loss, but also contributes to other diseases, such as cardiovascular disease and diabetes. We will find new methods to inhibit a system in our own bodies that contributes to inflammation and gum disease and test the effects of these methods of inhibition in disease models. In this way, we hope to lessen the burden of gum disease on the Australian population.