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.
Commercialisation Of A Glycoprofiling Diagnostic Kit And Novel Therapies For Biofilm Related Respiratory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$203,050.00
Summary
Our preliminary studies have shown that a group of patients who suffer from chronic inflammatory disease and have bacterial biofilm identified on their mucosa have worse outcomes even after surgery. We have shown that they lack certain small protein and sugar molecules on their respiratory lining. We aim to use this technology as a diagnostic tool to aid the doctor in prescribing the appropriate treatment for these patients to prevent bacteria regrowing in their respiratory tract.
Development Of A Novel Orally Active Peptide For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$402,145.00
Summary
Chronic pain from damage to the nervous system is difficult to treat. A new type of drug has recently been developed from sea snail venom to treat chronic pain but is given by injection, which limits its use. Our research has developed a stable molecule that has analgesic activity when ingested. This proposal focuses on further testing to fully establish this molecule's therapeutic potential. This information can then attract a commercial partner to bring the new drug into general use.
The Analgesic Evaluation Of Novel Natural Products From The Australian Plant Barringtonia Acutangula
Funder
National Health and Medical Research Council
Funding Amount
$174,500.00
Summary
This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that wi ....This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that will allow for their pharmacological evaluation as potential analgesic drugs.Read moreRead less
A Novel Device To Improve Renal Blood Flow In Cardiorenal Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$198,900.00
Summary
The aim of this project is to assist in the development of a novel device to treat poor delivery of blood to the kidneys in conditions such as heart muscle weakness (chronic heart failure, CHF). Specifically we aim to build a prototype and test the device in a relevant animal model of CHF. Chronic heart failure is a major public health problem affecting >10% of the adult population over the age of 60 years. It is associated with high morbidity, mortality, frequent hospitalisation and major co ....The aim of this project is to assist in the development of a novel device to treat poor delivery of blood to the kidneys in conditions such as heart muscle weakness (chronic heart failure, CHF). Specifically we aim to build a prototype and test the device in a relevant animal model of CHF. Chronic heart failure is a major public health problem affecting >10% of the adult population over the age of 60 years. It is associated with high morbidity, mortality, frequent hospitalisation and major cost burden on the public health system. Weak heart muscle results in poor delivery of blood to the kidneys. Poor delivery to the kidneys activates circulating hormones which in turn further impair cardiac function by adverse effects on the heart. We have developed and patented a novel catheter based system for improvement of renal function via a purpose built device. Proof-of-concept studies have shown that the device should improve kidney blood flow in the setting of CHF. Given the huge public health problem of heart failure and the importance of the kidney in this setting, the commercial potential for a simple device that can be positioned via a catheter-based approach, permanently implanted is large. The device is currently being constructed by the Monash University Department of Engineering where expertise exists with regard to biomedical devices and materials engineering. A series of proof-of-concept studies will then be performed in sheep, as the vasculature of the sheep roughly approximates the dimensions of man. Sheep with CHF will have the device inserted percutaneously into the aorta. Measurements will be made of renal artery flow, relevant circulatory hormones and ultrasound of the heart at baseline (pre-deployment) and following deployment. We believe the above studies (should they be successful) will be sufficient to constitute definitive proof-of-concept and thus allow the device to be commercialised, most likely by a licensing arrangement with a device company.Read moreRead less
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
Development Of Anti-CXCR2 Monoclonal Antibodies For Tumour Therapy
Funder
National Health and Medical Research Council
Funding Amount
$174,867.00
Summary
New therapies to treat cancers and inflammatory diseases are urgently required. Our aim is to develop a new treatment for cancer and inflammation, by blocking the chemokine receptor CXCR2 which is central to angiogenesis (blood vessel growth) and inflammation. We have produced a highly effective monoclonal antibody (mAb) inhibitor of CXCR2, that is suitable for preclinical and clinical development. The project aims to examine the efficacy of this mAb in mouse tumour models and inflammation.
Mechanical Mobility Of The Thorax For Continuous Determination Of Lung Gas Volume
Funder
National Health and Medical Research Council
Funding Amount
$165,000.00
Summary
Percussion is a valuable clinical method for physical examination of parts of the body. A sharp tap (impulsive force) is applied to the body wall and the sound radiated in response is observed. This sound may be dull (over liver) or stony dull (pleural effusion), or resonant (over normal lung) or hyper-resonant (over bowel). While the variation in radiated sound is not fully understood, it is apparent that the presence of gas, which is highly compliant, increases mobility of the overlying tissue ....Percussion is a valuable clinical method for physical examination of parts of the body. A sharp tap (impulsive force) is applied to the body wall and the sound radiated in response is observed. This sound may be dull (over liver) or stony dull (pleural effusion), or resonant (over normal lung) or hyper-resonant (over bowel). While the variation in radiated sound is not fully understood, it is apparent that the presence of gas, which is highly compliant, increases mobility of the overlying tissue and allows it to resonate; where the sub-tissue is largely fluid, tissue mobility is low and the percussive sound is dull. Percussion is useful for examining the adult chest and lung, but cannot for example be applied in infant intensive care as only limited impulsive force can be used, and the adult finger, which is both a coupling device and sounding board, is too large. As well, percussion requires skill and quiet conditions. Accordingly, we developed a device to measure mobility of the chest and other tissues in real time. The VibroPulse applies a known low-level force to the body surface and records the resultant velocity induced in the surface. The force is generated by a vibrating mass set in motion by an electromagnetic motor driven by pseudo-random noise. Tissue mobility, defined as velocity-force, is derived simultaneously across the frequency range, providing an easily interpreted quantitative output unaffected by ambient noise. This proposal has two aims we can achieve in 1 year: (1) to continue evaluating VibroPulse sensitivity to tissue composition, using symmetrical percussive sites on the human chest and abdomen that are dull on one side and resonant on the other, and the chest of anaesthetised animals with experimentally induced pneumothorax and lung collapse, two life-threatening conditions for which percussion is a key diagnostic method, and (2) to engineer a small device from our bulky prototype that is suitable for clinical use, in infants and adults.Read moreRead less
Ocular Implant For The Treatment Of Bacterial Endophthalmitis
Funder
National Health and Medical Research Council
Funding Amount
$483,446.00
Summary
We seek to develop an ocular implant for the treatment of bacterial endophthalmitis. The implant will be a small device that can be administered directly to the affected ocular cavity to release an antibiotic in a controlled manner to clear any infection. The implant will erode and leave no residue. It will be produced from a novel drug-polymer conjugate technology that allows polymer devices that comprise >50% drug to be made.