Control Of Refractive Error Through Ionically Driven Fluid Movements
Funder
National Health and Medical Research Council
Funding Amount
$208,600.00
Summary
Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oede ....Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oedema, retinal detachment and glaucoma). Currently there is no accepted pharmaceutical treatment for myopia though our studies in chick have provided the theoretical rationale and experimental data for a potential therapy and patent. This patent is now at the PCT stage and attests that changes in the abundance of the ions of the subretinal space control fluid movements across the retina to choroid and can be modulated therapeutically by diuretics to control fluid flow and hence axial growth and myopia. This application aims to take our current knowledge about fluid control in myopic chick into a mammalian model prior to preclinical trials in monkey. We anticipate it will take 1 year to establish the feasibility of diuretic control of experimentally induced myopic refractive errors in guinea pigs and the best drug and best the dosage range. These studies will contribute to the scientific understanding and bring the proposed pharmaceutical therapy for myopia in adults and children to a point of full commercialization. We believe that the results found in chick will have significance for early and late-onset myopia in humans as it is highly likely that the same mechanisms of ocular growth regulation operate throughout life.Read moreRead less
Rapid, Cost-effective, Diagnosis And Monitoring Of Multiple Sclerosis By Novel Multifocal Evoked Potential Methods
Funder
National Health and Medical Research Council
Funding Amount
$152,463.00
Summary
A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increas ....A new technology for concurrently stimulating both eyes, and recording thousands of responses from the brain, will be tested for its effectiveness in diagnosing and tracking progression in Multiple Sclerosis (MS), and the degree to which it complements Magnetic Resonance Imaging (MRI). Our understanding of MS has changed in recent years. It is now recognised to have two phases: an initial inflammatory phase, and a secondary progressive phase. The progressive phase produces the inexorable increasing disability of MS. MS only affects about 0.04% of Australians but the early onset of MS, the high cost of medication, and the prolonged period of disability, mean that the cost to Australia is about $2 billion pa. MRI quantifies the inflammatory phase well but is poorly correlated with the debilitating secondary progression. The common treatments for MS target the inflammatory phase but not the causes of secondary progression, which are unknown. Current diagnostic methods mean diagnosis can take years, meaning that patients can be denied treatment for some time. The applicants have published experiments on 50 MS patients and 27 normal subjects using a variant of the new method. Not only has it shown high diagnostic accuracy, but the new method seems to provide data on the progressive phase, suggesting strongly that it is complementary to MRI. The new method is also much cheaper to set up and run than MRI and so could provide cost-effective means for monitoring patient condition and testing new drugs that are effective against the progressive phase. The applicants have considerable experience commercialising diagnostic technologies, and are currently working with an Australian company developing new diagnostic hardware. That hardware has been adapted to perform the presently proposed experiments. Overall it is reasonable to assume that positive outcomes will be translated into economic and health benefits for Australians.Read moreRead less
An Inside-out Approach To Muscosal Vaccination: MAdCAM Targeting
Funder
National Health and Medical Research Council
Funding Amount
$174,250.00
Summary
The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the ....The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the gut (called MAdCAM) so that the vaccine is linked to an antibody against MAdCAM. Thus for the first time we believe that a parenteral vaccine ie. injected im or iv (bypassing the oral barriers) can induce mucosal immunity.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
Development Fo A Novel Treatment For Asthma: The Identification Of Lead Small Molecule Antagonists Of The IL-13/IL-13 Re
Funder
National Health and Medical Research Council
Funding Amount
$99,750.00
Summary
In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagoni ....In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagonists of IL-13Ra1 and to identify those suitable for development as novel asthma therapeutics.Read moreRead less
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
Novel Methods For Promoting Organ Development And Growth
Funder
National Health and Medical Research Council
Funding Amount
$390,203.00
Summary
A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of Colony Stimulating Factor (CSF-1). We have evidence that CSF-1 therapy can promote kidneys and lungs to continue development and maturation after birth. This exciting new finding allows for the application of CSF-1 therapy for both the treatment of premature babies and unborn babies with kidney defects.
Development Of Resonance Energy Transfer Technologies To Detect GPCR Heterodimer Complexes In Living Cells
Funder
National Health and Medical Research Council
Funding Amount
$205,555.00
Summary
G-protein coupled receptors are proteins at the surface of most cells in the body. They bind to drugs, transmitting signals into cells that change what cells are doing. Recent research indicates that different types of these proteins can interact with each other and when one of these protein combinations binds a drug, it acts differently to when the proteins act separately. The aim of our project is to find out which protein combinations exist and to find drugs that bind to them specifically.
Novel Soluble Guanylate Cyclase Activators For Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$474,087.00
Summary
Pulmonary hypertension (elevated blood pressure in the lungs) is a life-threatening condition with few treatment options. We have recently identified a new class of drug that may improve blood vessel function in the lungs and thereby provide a new drug for the management of this group of patients.