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
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
Assessment Of Bilateral Oedema By Bioelectrical Impedance Analysis
Funder
National Health and Medical Research Council
Funding Amount
$180,000.00
Summary
Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estima ....Swelling of tissue due to fluid accumulation, known as oedema, is one of the earliest signs of diseases such as kidney failure, burn injury or lymphedema. All of these are not uncommon conditions. Lymphedema, for example, is a common sequela of radiotherapy or surgery in the treatment of malignancies such as breast, uterine, and prostatic carcinoma. It is reported to occur in up to 40% of patients depending on the type of surgery and whether or not the patient received radiotherapy. It is estimated that at any time 100000 women are suffering from post- mastectomy lymphedema in Australia alone. Treatment of breast cancer alone therefore, given the incidence of the disease, produces a large at-risk population. Add to this other causes of oedema and the magnitude of the problem becomes clearly apparent. The presence of chronic oedema is often a disfiguring and disabling disorder, usually accompanied by pain, recurrent infection, reduced mobility and impaired function. In acute oedema the problem often resolves with recovery from the underlying pathology. In chronic oedema, progression may be arrested by early intervention including complex physical therapy (exercise regimen, compression bandaging, and massage) which is effective in reducing limb volume, in improving the quality of life, function and body image of patients. Although the assessment of oedema is clearly of clinical importance, relatively few objective and accurate techniques for its measurement exist. Research conducted over the past decade by the applicants has pioneered the Use of Bioelectrical Impedance Analysis for the assessment of lymphedema. This study aims to translate this basic research into clinical practice. Sensitivity and specificity studies will establish normative and threshold values for impedance measurements that can be used as presumptive indicators of oedema. User friendly technology and equipment suitable for clinical use will be developed which should improve treatment therapies.Read moreRead less
We will conduct a clinical trial of the effectiveness of a continuous auditory display of an anesthetized patient's respiratory status. Expired carbon dioxide monitoring has helped reduce respiratory incidents since its widespread introduction in the late 1980s, but a continuous auditory display of respiratory status may reduce incidents further. We will conduct a clinical trial with 10 anaesthetists of continuous auditory respiratory monitoring. Successful outcome may lead to commercial uptake.
Development And Clinical Evaluation Of A Depth Of Anaesthesia Monitor
Funder
National Health and Medical Research Council
Funding Amount
$424,785.00
Summary
Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a g ....Waking up during surgery (awareness under anaesthesia) is a frightening reality for some patients. Although uncommon (occurring in about 1 in 1000 operations), it remains one of the main concerns of patients before their surgery. Recent studies (including our own) have demonstrated that processed EEG monitoring using bispectral index (BIS) can markedly reduce the risk of awareness. Other EEG monitors are being developed, but each have weaknesses. As approximately two million Australians have a general anaesthetic each year, about 2000 will suffer an episode of awareness. More than 60 million people around the world have an anaesthetic, and so the problem is substantial. This suggests the potential benefits (health outcomes, commercial gains) are very great. In 2000 less than 5% of US hospitals used BIS monitoring; the current figure in the US is about 69% of the best-rated hospitals (US News and World Report) and 78% of teaching hospitals. A similar rapid growth is occurring in Australia and Europe. We are working with a successful Australian Company (Compumedics Ltd) to develop a better awareness monitor. We plan studies in groups of patients have surgery.Read moreRead less
A Novel Treatment For Ameliorating Retinal Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$366,685.00
Summary
Retinal vascular disease is a leading cause of blindness and is currently treated by laser photocoagulation surgery. Although successful, this treatment is associated with serious side effects. Recently, Ellex Pty has developed a novel laser called the 2RT laser that is likely to be effective without the accompanying side effects. This study will allow examine the effect of the 2RT laser in animal models of retinal vascular disease so as to complete preclinical development of this laser.
Development Of A Smart Arthroscopy System And Prototype Probe For Joint Tissues
Funder
National Health and Medical Research Council
Funding Amount
$230,632.00
Summary
This project relates to the ever growing use of arthroscopy in the management of joint defects. An innovative probe that will combine all the molecular, microstructural and biomechanical characteristics of joint articular cartialge and bone for the purposes of diagnosis, treatment, treatment-related decisions, comparison of the effectiveness of treament methods and post treatment evaluation will be developed. This system will produce spin-offs for artrhoscopy of other soft tissues and bodies.
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.
Development Of Anti-metastatic And Tumour Targeting Reagents By Design Of Inhibitors To Specific Eph/ephrin Cell-cell
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (E ....Metastatic disease, malignant melanoma in particular, is a health issue of considerable global importance with 1,000 fatal melanoma cases- year in Australia alone. While progress has been made on prevention and early diagnosis, no curative treatment exists for stage IV melanoma. Tumour progression and the acquisition of metastatic competence primarily reflect dysregulation of cell adhesion and cell motility rather than proliferation and survival. In this context, Eph receptor tyrosine kinases (Ephs) and their membrane-bound ephrin ligands are crucial mediators of cell adhesion and motility and are notably overexpressed in metastatic tumours rather than primary (benign) lesions5. Our laboratories were the first to identify EphA3 7, and one of the first to isolate its ligand, ephrin-A5. EphA3 was isolated from acute lymphoblastoid leukemia and malignant melanoma patients, where increasing expression levels correlate with metastatic progression. Soluble, non-clustered forms of Ephs and ephrins are effective inhibitors of Eph activity 3 and provide opportunities to generate specific drugs for cancer therapy. We now propose a research and development program for the development of EphA3-specific drugs and their production for pre-clinical and clinical evaluation for placement onto a national and international market.Read moreRead less