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.
Targeting Neuroinflammatory Pathways As Novel Treatments For Dementia
Funder
National Health and Medical Research Council
Funding Amount
$600,116.00
Summary
Australia has a rapid increase in its ageing population, and consequently an increase in detrimental age-related dementia and neurodegenerative diseases which are a major healthcare burden. Current treatments for diseases such as Alzheimer’s, Parkinson’s and Huntington’s are inadequate and there is a desperate need for new treatments. I have unique access to molecules that target two novel mechanisms for neurodegenerative diseases. This fellowship will explore their therapeutic potential.
Targeting Complement C5a Receptor 2 As A Disease-modifying Treatment For Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$636,329.00
Summary
Motor neuron disease (MND) is a devasting terminal condition that has no effective treatment. We have identified a novel drug which inhibits an immune protein that can potentially treat MND. In this project we will test this drug in rodent models of MND, and validate its effectiveness in relevant MND immune cells. Ultimately, this project will identify a new potential drug for MND.
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.
Preclinical Development Of A Humanised Antibody To C5aR.
Funder
National Health and Medical Research Council
Funding Amount
$124,875.00
Summary
Complement factor C5a is one of the most potent inflammatory mediators in the body. We have developed a monoclonal antibody that blocks the C5a receptor in vitro, and completely shuts down disease in a mouse model of rheumatoid arthritis. We plan to develop this promising new antibody into a potent therapy to treat a range of chronic and acute inflammatory diseases. The antibody has been humanised and this will be tested in three models of inflammation (rheumatoid arthritis, sepsis and colitis) ....Complement factor C5a is one of the most potent inflammatory mediators in the body. We have developed a monoclonal antibody that blocks the C5a receptor in vitro, and completely shuts down disease in a mouse model of rheumatoid arthritis. We plan to develop this promising new antibody into a potent therapy to treat a range of chronic and acute inflammatory diseases. The antibody has been humanised and this will be tested in three models of inflammation (rheumatoid arthritis, sepsis and colitis) to determine the efficacy of the antibody, safety, the most effective dose, timing and route of administration. These studies are a necessary prelude to human clinical trials, which we hope to perform in approximately 24 months.Read moreRead less
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.
Evaluation Of Orally Active Anti-inflammatory C5a Receptor Antagonists In A Transgenic Rat Motor Neurone Disease Model
Funder
National Health and Medical Research Council
Funding Amount
$533,578.00
Summary
Motor neurone disease is a rapidly progressive and incurable disease, usually ending in death within 3-5 years of diagnosis. The disease usually arrives without warning, and results in a progressive loss of muscle control. There is no effective treatment, and available drugs increase life span by a few weeks at best. There is evidence that the disease involves an inflammatory component, but available anti-inflammatory drugs are ineffective. We have developed a new class of anti-inflammatory drug ....Motor neurone disease is a rapidly progressive and incurable disease, usually ending in death within 3-5 years of diagnosis. The disease usually arrives without warning, and results in a progressive loss of muscle control. There is no effective treatment, and available drugs increase life span by a few weeks at best. There is evidence that the disease involves an inflammatory component, but available anti-inflammatory drugs are ineffective. We have developed a new class of anti-inflammatory drugs, known as C5a antagonists, and in preliminary experiments have shown they are therapeutically effective in a transgenic rat model of motor neurone disease. We propose to investigate in more detail how these drugs work in the rat model, and demonstrate that a specific inflammatory pathway, which we can now block, is responsible for some of the disease's progression. This work may lead to an entirely new class of drugs being used to treat patients with this drastic disease.Read moreRead less