Development Of Novel And Selective Anticancer Drugs Derived From Cysteine.
Funder
National Health and Medical Research Council
Funding Amount
$264,250.00
Summary
In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tum ....In the next few years cancer is projected to become the leading cause of death in industrialised countries. Cancer chemotherapy currently relies on destruction of tumours by toxic drugs that indiscriminately kill all cell types, resulting in side effects that limit treatment. In the 21st century new cancer drugs will more effectively destroy malignant tumour cells without damaging normal cells. The R and D herein will value-add to our discovery of a new class of potent and orally active anti-tumour drugs that possess unusually high selectivity in acting on cancer cells without killing normal human cells. Our current proof of concept will be turned into a drug development candidate that will improve our negotiating position with commercial partners.Read moreRead less
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
Stage II In The Development Of Eph/ephrin Based Tumor Targeting Reagents: Optimisation Of Drug Efficacy And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$204,125.00
Summary
In the final stage of cancer, including melanoma, tumor cells gain the ability to spread, a process called metastasis. Altered communication between cancer and normal cells is one of the causes of this invasive characteristic. We have started the development of novel agents that target and modulate proteins on the cell surface that control these properties and are found in metastatic tumors. We propose to refine the targeting and killing properties of these agents for early clinical testing.
Development Of A Computer-based Retinal Imaging Program For Identification Of People At Risk Of Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$254,714.00
Summary
Cardiovascular disease is the leading cause of death and imposes an enormous financial and healthcare burden on the Australian community. This project will develop and deliver a novel clinical prediction tool, incorporating retinal vascular imaging and assessment, to improve identification of asymptomatic people who are at high risk of cardiovascular disease at an early stage, allowing implementation of preventative strategies and medical interventions to effectively prevent CV disease.
Development And Pre-clinical Evaluation Of G-DSF Inhibitors For Inflammatory Joint Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,329.00
Summary
G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in expe ....G-CSF was originally identified as a cytokine regulating the production of neutrophils and haemopoietic stem cells from the bone marrow and it is currently used clinically for these properties in bone marrow transplant patients around the world. Anti-cytokine therapy with TNF blockade has recently been introduced for the treatment of rheumatoid arthritis. However, not all patients respond to TNF inhibition. We have gathered extensive data which shows that G-CSF also promotes inflammation in experimental models of inflammatory joint disease. We propose to develop inhibitors of G-CSF as a novel form of anti-cytokine therapy for inflammatory joint disorders, such as rheumatoid arthritis.Read moreRead less
GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
A Novel Method For The Early Detection Of Cardiovascular Disease Through The Direct Measurement Of Tissue Wall Elasticit
Funder
National Health and Medical Research Council
Funding Amount
$196,000.00
Summary
Changes in the structure and function of blood vessels are an early stage in the development of arterial disease. A simple means of assessing this damage will allow for early detection of arterial disease and will provide a tool for monitoring outcomes of treatment and preventive medicine. We have developed a novel method for measuring vessel wall displacement throughout the cardiac cycle. This study aims to provide proof of principle data through the validation of these measurements against the ....Changes in the structure and function of blood vessels are an early stage in the development of arterial disease. A simple means of assessing this damage will allow for early detection of arterial disease and will provide a tool for monitoring outcomes of treatment and preventive medicine. We have developed a novel method for measuring vessel wall displacement throughout the cardiac cycle. This study aims to provide proof of principle data through the validation of these measurements against the physical properties of the vessel and application of the technique to a clinical setting.Read moreRead less
Innovations For Better Cardiovascular Prevention In Primary Care
Funder
National Health and Medical Research Council
Funding Amount
$294,285.00
Summary
The goal of this project is to take a new concept for cardiovascular disease management through the proof-of-concept stage and deliver a novel model for cardiovascular disease management. When proven, the application of this new process for service delivery will provide a low-cost way of closing the gap between guideline recommendations and current management of vascular disease in Australian primary care settings.
Prevention Of Neuron Death By Targeted Gene Delivery
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Neurotrophic factors are potent proteins that have the ability to keep nerves alive. They have therefore been used in clinical trials to treat motor neuron disease, but without success. A major reason for this appears to be the way in which the neurotrophic factors are delivered. Direct injections into the blood stream are a convenient way of getting these large proteins into the bloodstream, but this is not their normal mode of action. These proteins are normally provided by cells adjacent to t ....Neurotrophic factors are potent proteins that have the ability to keep nerves alive. They have therefore been used in clinical trials to treat motor neuron disease, but without success. A major reason for this appears to be the way in which the neurotrophic factors are delivered. Direct injections into the blood stream are a convenient way of getting these large proteins into the bloodstream, but this is not their normal mode of action. These proteins are normally provided by cells adjacent to the nerves. We have designed a system that more closely resembles this physiological mode of action which involves the delivery of neurotrophic factor genes, via the bloodstream, to the affected nerves. Once inside the nerves the factors are produced on site and, following their secretion, act locally and directly on the injured nerves.Read moreRead less