Development Of New Anti-fibrotic Drugs For Prevention Of Diabetic Nephropathy.
Funder
National Health and Medical Research Council
Funding Amount
$133,800.00
Summary
Diabetic kidney disease is the leading cause of kidney failure in the developed world. Currently there is no treatment that reduces the excessive scarring that leads to kidney failure. This project aims to test whether a series of novel compounds that have been specifically designed to reduce scarring can prevent diabetic kidney disease.
Spectrometer Module For Surface Enhanced Raman Scattering Spectroscopy In Glucose Analysis
Funder
National Health and Medical Research Council
Funding Amount
$385,151.00
Summary
Scientists have developed a number of incredibly powerful and sophisticated techniques to identify chemicals and measure their concentrations in the laboratory. However, it remains a major challenge to perform these measurements under everyday circumstances. For example, surface-enhanced Raman scattering (SERS) has gained widespread recognition as a technique for trace chemical detection, but it remains confined to a small number of specialist laboratories. For this reason, Dr Paul Stoddart at S ....Scientists have developed a number of incredibly powerful and sophisticated techniques to identify chemicals and measure their concentrations in the laboratory. However, it remains a major challenge to perform these measurements under everyday circumstances. For example, surface-enhanced Raman scattering (SERS) has gained widespread recognition as a technique for trace chemical detection, but it remains confined to a small number of specialist laboratories. For this reason, Dr Paul Stoddart at Swinburne University of Technology recognised a need for more practical SERS probes for field applications. His team has now developed a proprietary SERS probe, based on an optical fibre that is little thicker than a hair. These optical fibres can form the core element of field-portable SERS spectrometers. This work has recently been boosted by the discovery in the United States that SERS can be used to monitor glucose in blood. The development of a continuous glucose monitor has long been a holy grail of sensor research, because of the millions of diabetes sufferers who regularly perform the painful finger prick test. For SERS to provide a practical solution to glucose monitoring, it is recognised that SERS optical fibres are needed for minimally invasive probes. With support from Biopharmica and the Diabetes Australia Research Trust, Dr Stoddart's team has now demonstrated that sensitive SERS probes can be produced in large quantities. The next objective is to develop a prototype low-cost SERS spectrometer for use as part of a continuous glucose monitoring system. This will require the development of a laser source and spectroscopic system that can interface to the SERS probes. It is proposed to use an Australian designed and manufactured laser system based on a low-power narrow-linewidth laser diode. The project plans to bring together Swinburne University, OptoTech and Grey Innovation in order to develop a commercially scaleable and robust device.Read moreRead less
Development Of Small Molecule IRAP Inhibitors For Treating Memory Deficits
Funder
National Health and Medical Research Council
Funding Amount
$369,898.00
Summary
We have identified a series of small molecule compounds based on their ability to inhibit the catalytic activity of a protein, IRAP using a computer model of IRAP to screen chemical libraries. This research proposal aims to investigate the properties of these compounds and their ability to treat Alzheimer's dementia. At the conclusion of this project, we will have 2 families of lead compounds suitable for development into a new class of therapeutic agents for treating Alzheimer's disease.
Development Of Small Molecule Inhibitors Of IRAP - Potential Use For The Treatment Of Memory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$195,450.00
Summary
This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusio ....This research project provides proof of concept that IRAP is a suitable target for use in the development of a new class of clinically valuable cognitive-enhancing agents. We have recently Identified a family of small molecule compounds that inhibited the catalytic activity of the enzyme using a molecule model of IRAP to screen virtual libraries. This research proposal aims to validate that this family of compounds have memory-enhancing properties by acting specifically on IRAP. At the conclusion of this project, we will have elucidated important information on the specificity of the memory effects and the structure activity relationship of this family of compounds. We will have identified and characterised a lead compound for development into a new class of cognitive enhancers.Read moreRead less
Targeting Protein Kinase C In Diabetes Management Using Novel Polyunsaturated Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
PKC regulates a diverse range of cellular processes in an isozyme-specific manner. There is strong recent evidence to implicate PKC, especially PKC _, in mediating the actions of glucose in diabetes. This includes the action of glucose in renal glomeruli, retina, aorta and heart of diabetic animals and in cultured cells from these organs. More importantly, inhibition of PKC_ with the PKC_-specific inhibitor, LY333531, blocks the actions of glucose. Recently, our research group designed and synth ....PKC regulates a diverse range of cellular processes in an isozyme-specific manner. There is strong recent evidence to implicate PKC, especially PKC _, in mediating the actions of glucose in diabetes. This includes the action of glucose in renal glomeruli, retina, aorta and heart of diabetic animals and in cultured cells from these organs. More importantly, inhibition of PKC_ with the PKC_-specific inhibitor, LY333531, blocks the actions of glucose. Recently, our research group designed and synthesised a family of novel polyunsaturated fatty acids. One of these, MP5 (_-oxa- 21:3n-3), inhibited high glucose-induced activation of PKC? in cultured mesangial cells as well as in glomeruli of diabetic rats in a relatively selective manner. The overall aim of this proposal is to evaluate the potential for a chemically engineered novel polyunsaturated fatty acid, MP5 (_-oxa-21:3n-3), to treat pathogenesis associated with diabetes by targeting the PKC system. The specific aims are to: 1. Characterise the effects of MP5 on glucose- or advanced glycosylation end product-stimulated activation of protein kinase C (PKC). 2. Determine whether esterification of MP5 into diacylglycerol is essential for the action of MP5 3. Investigate whether MP5 is efficacious at preventing the actions of glucose in vitro e.g. glucose stimulated TGF_ production in mesangial cells, and in vivo in streptozotocin-diabetic rRead moreRead less
Development Of Inhibitors Of PKCzeta For Targeting Vascular Leak
Funder
National Health and Medical Research Council
Funding Amount
$335,113.00
Summary
Vascular leak (permeability) is a chief pathophysiological mechanism of many inflammatory diseases and cancer. Effective methods of reducing vascular permeability are likely to reduce or prevent morbidity. At present there are no potent broad spectrum inhibitors of vascular permeability. This application focuses on the development of such inhibitors.
Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$157,375.00
Summary
Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown ....Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.Read moreRead less
Development Of A Protein Tyrosine Kinase Inhibitor For Modification Of GAG Chains And Prevention Of Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$389,778.00
Summary
The major health issue in Australia is vascular and cardiovascular disease resulting from obesity and diabetes. Whilst prevention strategies based on lifestyle changes are preferable, treating cardiovascular risk factors with the latest drugs has been shown to produce significant benefits. There is however a large group of patients who still acquire cardiovascular disease in spite of drug therapy. New therapies are required and these will most likely target blood vessels directly. We have identi ....The major health issue in Australia is vascular and cardiovascular disease resulting from obesity and diabetes. Whilst prevention strategies based on lifestyle changes are preferable, treating cardiovascular risk factors with the latest drugs has been shown to produce significant benefits. There is however a large group of patients who still acquire cardiovascular disease in spite of drug therapy. New therapies are required and these will most likely target blood vessels directly. We have identified a biochemical mechanism that represents a prime target for vascular wall directed therapy and we aim to exploit the therapeutic potential of this pathway by developing a drug to prevent atherosclerosis. A group of large molecules which have recently received increasing attention are the proteoglycans, combined protein-sugar molecules which are heavily coated with negatively charged groups. The binding and retention of lipids in the wall of the blood vessel is the main cause of atherosclerosis. Specifically, the length of the sugar (GAG) chains on the proteoglycans determines the binding of the lipids. We have discovered a new class of inhibitors which directly target proteoglycan synthesis in the vessel wall and greatly reduce the interaction between proteoglycans and lipids. We wish to demonstrate the efficacy of our compound in an animal model with the aim to produce a marked reduction in the rate and extent of development of atherosclerosis. This would lay the foundation for the compound to be taken into human safety trials and subsequently develop an agent for the prevention of atherosclerosis and a thus a reduction in cardiovascular disease.Read moreRead less
Development Of A Prototype Production System For Optical Fibre Diagnostic Probes
Funder
National Health and Medical Research Council
Funding Amount
$191,598.00
Summary
Advances in nanotechnology have led to new techniques for the precise fabrication of nanometre scale structures. A recent breakthrough by the applicants now allows high-quality nanostructures to be stamped onto the tip of low-cost optical fibre probes. When coated with silver, these sensitive probes can be used for continuous monitoring of blood glucose in diabetics and in critical care situations. This project aims to develop a prototype manufacturing system for optical fibre glucose probes.