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
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.
Oxidation Of Mismatch: A New Concept For Mutation Detection Which Avoides A Separation Method In Mutation Scanning
Funder
National Health and Medical Research Council
Funding Amount
$143,000.00
Summary
Detection of faults (mutations) in genes is expensive but essential for proper genetic health care. Because of the cost of such tests many people are not diagnosed either through diagnostic labs or research of the cost of such tests many people are not diagnosed either through diagnostic labs or research projects. Such research projects are inhibited due to the complexity of the current methods. Current methods are complex and expensive, especially looking for a possible fault, due to what is ca ....Detection of faults (mutations) in genes is expensive but essential for proper genetic health care. Because of the cost of such tests many people are not diagnosed either through diagnostic labs or research of the cost of such tests many people are not diagnosed either through diagnostic labs or research projects. Such research projects are inhibited due to the complexity of the current methods. Current methods are complex and expensive, especially looking for a possible fault, due to what is called a preparation step on complex and expensive equipment. We will develop and commercialise a simpler test because separation is avoided.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
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
Development Of A Multiplex Assay For The Identification Of Women At Risk Of Preterm Labour.
Funder
National Health and Medical Research Council
Funding Amount
$202,350.00
Summary
Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days ....Preterm birth (ie birth before the 37th week of gestation) is the most significant problem facing contemporary clinical obstetrics in the developed world and occurs in approximately 5% to 12% of all deliveries. Being born too early is the major cause of perinatal morbidity and mortality. Data from Australia indicate that each year, more than 17,000 babies will be born prematurely. Of these infants, over 10,000 will suffer respiratory complications and about 1300 will die during the first 21 days of life. The sickest and most premature of these infants require admission to a Neonatal Intensive Care Unit in a tertiary hospital. Aside from the medical implications of premature delivery, there is also a considerable fiscal challenge to society. While treatments for the prevention of labour have improved considerably over the past decade, current screening tests of preterm labour (ie Fetal Fibronectin test) are unreliable and have poor positive predictive values. The principal objective of this project is to develop and deliver a multiplex assay for the prediction and diagnosis of human preterm labour. Through the successful application of our own proteomic discovery programmes using both ovine and human cervico-vaginal fluid samples, we have identified several new protein markers of labour. Having completed this Phase 1 biomarker trial and established proof-of-concept, we are now well positioned to initiate a Phase 2 biomarker trial to determine reliable estimates of assay sensitivity and specificity. This project targets the development of a new diagnostic to meet a recognised market gap. Delivery of such a test will create a new market in pregnancy-based clinical diagnostics and significantly impact on improving health care and quality of life for many preterm babies. Should the project be completed as detailed and mitigate some of the risk of commercial development, it would then be realistic to seek substantial funding from the private sector.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
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