Protease Activated Receptor 2 Antagonist In Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,347.00
Summary
The immune response to infection involves a network of proteins that produce an inflammatory response. Sometimes this response is prolonged or uncontrolled and can lead to a large number of inflammatory and other diseases. We have discovered a class of drugs that can bind to a particular protein on the surface of human cells and control this inflammatory response. This property has the potential to treat a wide range of inflammatory and other diseases in humans.
Development Of A Vaccine For Genital Chlamydial Infection
Funder
National Health and Medical Research Council
Funding Amount
$207,551.00
Summary
Genital Chlamydia infections are the most common sexually transmitted infection in Australia with annual health costs of 90-160 million dollars. Infection rates in 15-29 olds are increasing at 15-20% per year. Antibiotics are currently the treatment of choice, however antibiotic resistance is increasing and most infections are asymptomatic and not treated in the absence of screening programs. This project aims to develop a genital Chlamydia vaccine using a combination of novel antigens.
Development Of Recombinant RsolCD39-PSGL As A Novel Therapeutic With Anti-thrombotic And Anti-inflammatory Effects
Funder
National Health and Medical Research Council
Funding Amount
$186,367.00
Summary
Heart disease and stroke are due to a narrowing of arteries followed by occlusion, due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. The currently available drugs are often limited by the adverse reaction of bleeding. We will investigate the efficiency of a new drug to prevent clot formation and inflammation.
Developing Anti-Inflammatory Drugs Based On Inhibition Of A Human Enzyme
Funder
National Health and Medical Research Council
Funding Amount
$160,000.00
Summary
Human secretory phospholipases A2 have been associated with inflammatory diseases for many years, yet very few truly potent inhibitors of the human enzymes sPLA2 (isoforms IIa, V or X) are known due to a range of problems relating to the lipid nature of substrates, unavailability of enzymes, enzyme assays that do not correlate with in vivo data. Although there remains controversy about which enzyme is responsible in vivo for degrading membrane phospholipids to inflammatory mediators like arachid ....Human secretory phospholipases A2 have been associated with inflammatory diseases for many years, yet very few truly potent inhibitors of the human enzymes sPLA2 (isoforms IIa, V or X) are known due to a range of problems relating to the lipid nature of substrates, unavailability of enzymes, enzyme assays that do not correlate with in vivo data. Although there remains controversy about which enzyme is responsible in vivo for degrading membrane phospholipids to inflammatory mediators like arachidonate, PAF, prostaglandins, leukotrienes, etc. there is a consensus that blockade of phospholipid metabolism would represent a major advance on NSAIDs as antiinflammatory agents. No sPLA2-IIa inhibitor is available yet in man. We aim to create an attractive data package showing proof of concept for a potent new type of antiinflammatory drug. This data will give us an improved negotiating position in our commercialisation of a new drug with potential multi-billion dollar markets as diverse as arthritis, asthma, reperfusion injury, organ transplantation and many other currently intractable human ailmentsRead moreRead less
Development And Biological Evaluation Of Cytokine Macrophage-migration Inhibitor (MIF) Non-Steroidal Antagonists
Funder
National Health and Medical Research Council
Funding Amount
$85,000.00
Summary
The cytokine macrophage-migration inhibitory factor (MIF) has a broad range of pro-inflammatory effects in the innate and adaptive immune system. CIA’s lab has demonstrated the potential importance of MIF in the pathology of chronic inflammation via studies in models of rheumatoid arthritis (RA). Similarly to other chronic inflammatory diseases, MIF is overexpressed in human RA, and induces activation of key pathological processes in RA cells. Moreover, antagonism of MIF with mAb profoundly inhi ....The cytokine macrophage-migration inhibitory factor (MIF) has a broad range of pro-inflammatory effects in the innate and adaptive immune system. CIA’s lab has demonstrated the potential importance of MIF in the pathology of chronic inflammation via studies in models of rheumatoid arthritis (RA). Similarly to other chronic inflammatory diseases, MIF is overexpressed in human RA, and induces activation of key pathological processes in RA cells. Moreover, antagonism of MIF with mAb profoundly inhibits models of RA and other inflammatory diseases, confirming MIF as a therapeutic target in human inflammatory disease. The X-ray crystal structure of MIF has been published and the putative active site fully characterised. We have deduced structural features of MIF that reveal aspects of the structural complementarity of host-guest affinity. This information has been used in the synthesis of new compounds to antagonise MIF. We have designed, synthesised and tested several classes of compounds, which have shown activity from milli to nano-molar levels in novel in-house in vitro bioassays.Read moreRead less
There is an unmet need for safe and effective anti-inflammatory drugs. Because P38 MAPK intracellular signalling modulates multiple pro-inflammatory cytokine actions, it appears to be an ideal candidate pathway. P38 inhibitors have been limited by their toxicity within hepatocytes. The aim of this program therefore is to develop agents with enhanced P38 MAPK inhibitory effects as well as reduced liver toxicity based on known structure activity relationships.
Development Of A Highly Potent, Fully Human Anti-GM-CSF Monoclonal Antibody
Funder
National Health and Medical Research Council
Funding Amount
$334,000.00
Summary
Many diseases, such as arthritis, have unwanted inflammatory reactions. Better drugs are needed to control inflammation. A powerful antibody to a significant pro-inflammatory cytokine will be generated; this antibody will be especially designed so that it will not be rejected by patients. Because of its properties it will cost the community less than similar therapeutics. Because inflammatory diseases are common many patients will benefit from our therapeutic.
Development Of An Anti-GM-CSF Antibody For Treatment Of Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$283,000.00
Summary
The aim of this project is to develop assays for the evaluation of the efficacy and safety of an anti-GMCSF neutralizing antibody in a Australian first-in-man clinical trial in patients with severe rheumatoid arthritis (RA). This chimeric antibody has been developed by the Ludwig Institute for Cancer Research, Melbourne Branch, in conjunction with KaloBios Pharmaceuticals, Inc., USA. It is intended to use the assays developed in this project to facilitate commercial development of this antibody, ....The aim of this project is to develop assays for the evaluation of the efficacy and safety of an anti-GMCSF neutralizing antibody in a Australian first-in-man clinical trial in patients with severe rheumatoid arthritis (RA). This chimeric antibody has been developed by the Ludwig Institute for Cancer Research, Melbourne Branch, in conjunction with KaloBios Pharmaceuticals, Inc., USA. It is intended to use the assays developed in this project to facilitate commercial development of this antibody, and result in the development of an improved treatment for this devastating disease.Read moreRead less
Development And Evaluation Of Novel Anti-inflammatory Products Derived From An Indigenous Medicinal Plant
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
This collaborative project between researchers at the University of South Australia and Indigenous traditional owners from Northern Kaanju homelands (Cape York Peninsula, Qld) will develop and evaluate products derived from the Northern Kaanju medicinal plant Dodonaea polyandra. Extracts of the plant and novel compounds isolated from it have anti-inflammatory activity. These have the potential to be used in inflammatory diseases such as dermatitis, arthritis and inflammatory bowel disease.
Performance And Safety Testing Of The BioQ Cardiac Assist System In A Chronic Ovine Heart Failure Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$142,800.00
Summary
This proposal will test a novel cardiac assist system in safety and performance studies using a chronic sheep heart failure model. This device has been tested in cardiovascular simulators and in an acute animal model showing attractive proof-of-concept data. Specifically, the device increased left coronary artery blood flow and reduced aortic pulse and mean pressures using our novel self-powered fully implantable stand alone device, a potential therapy treatment for heart failure.