Bisphosphonate Therapy With Zoledronate Or Tenofovir Switching To Improve Low Bone Mineral Density In HIV-Infected Adults: A Strategic, Randomised Trial
Funder
National Health and Medical Research Council
Funding Amount
$716,300.00
Summary
Most HIV+ Australians receive tenofovir, a ‘preferred’ drug in all HIV treatment guidelines, and may do for decades, as HIV therapy is lifelong and because there are very few new HIV drugs. 40% of HIV+ adults have low bone density and HIV+ adults experience more fractures. Of all HIV drugs, tenofovir causes the most bone loss. This trial compares two approaches: a drug to improve bone density and switching tenofovir to another drug. This ‘treat versus switch’ approach is a world-first for HIV.
A Novel Portable System For Day And Night Closed Loop Automated Insulin Delivery In The Patient With Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$251,133.00
Summary
For patients with Type 1 Diabetes, improved glucose control has been shown to reduce the development of diabetes complications. Although advances have been made in therapy, most people with diabetes do not achieve optimal treatment targets and the burden of care is high. Technologies now exist that allow the development of automatic insulin therapy and the artificial pancreas. These experiments will test a novel portable system that represents a significant step advancing toward this goal.
Validating A New Model For Growth Hormone Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its anabolic actions. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and ageing. The hormone exerts these actions through its receptor, which is a class1 cytokine receptor, similar to many receptors important in regulating immunity, inflam ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its anabolic actions. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and ageing. The hormone exerts these actions through its receptor, which is a class1 cytokine receptor, similar to many receptors important in regulating immunity, inflammation, metabolism and cancers. In principle, if we can find out how the GH receptor works, this information would help in designing drugs to treat many immune and inflammatory disorders. With current NHMRC support we have developed a model which describes how GH activates the receptor at a molecular level. The model involves two pre-associated receptors at the cell surface binding to the hormone, with the result that the receptors are rotated relative to each other, and this brings the two JAK2 signalling units attached tothe receptor inside the cell into alignment, so they can activate each other. We can activate the receptor without hormone by artificially rotating it. This model is a prediction based on several techniques, but lacks proof of rotation. There are also a number of issues relating to the need for rigidity in the receptors, so the torque can be transmitted into the cell, since many believe there is no rigidity just above the membrane. We predict there is , but need to prove this. This information is vital for designing small orally active mimics of growth hormone, and for developing GH antagonists, likely to be useful for breast and colon cancer. Finally, we have evidence that the specificity of receptor signalling can be changed by mutating the outer part of the receptor (novel). We believe this can be used to change the activity spectrum of GH, hence decrease side effects, by developing analogs which activate one pathway or the other.Read moreRead less
Molecular Determinants Of Advanced Disease In Ovarian Granulosa Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$612,244.00
Summary
Granulosa cell tumours of the ovary (GCT) represent 5-10% of malignant ovarian cancers. They are distinct from the more common epithelial tumours and although considered to have a much better prognosis, they have a propensity to late recurrence. Recurrent or aggressive GCT have a poor prognosis. These studies will investigate the molecular basis of recurrence and aggressive behaviour in GCT. This will provide both prognostic information and also potential therapeutic targets.
Improving The Lives Of Young People With Type 1 Diabetes Using State-of-the-Art Therapies
Funder
National Health and Medical Research Council
Funding Amount
$2,599,598.00
Summary
T1D profoundly affects the lives of an increasing number of young people and their families. H The proposed centre acknowledges these challenges and recognises the urgent need for a comprehensive and holistic approach involving a broad range of expertise, methodologies and collaboration. The centre will utilize clinical expertise of the CI’s, generating new knowledge for the successful development and use of technology in closed loop and semi-closed systems in young people with T1D.
Reversal Of Diabetes In A Humanised Mouse Using A Clinically Applicable Vector System
Funder
National Health and Medical Research Council
Funding Amount
$842,173.00
Summary
Somatic gene therapy is one of the strategies that is being considered to cure Type I diabetes. Specifically, we wish to engineer liver cells to replace beta cell function. The aim of this project is to design a clinically-applicable protocol for the reversal of diabetes using a recombinant adeno-associated vector that delivers genes to human livers with high efficiency showing long term expression without pathogenicity and immunogenicity following a simple intra-peritoneal injection.
Hypothalamic Signalling In Cortical And Trabecular Bone Anabolic Activity
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but the ....Osteoporosis is a disease associated with an exponential rise in the number of fractures in the elderly. These fractures are so common that around 1 in 3 women and 1in four men will be affected. They cause pain, disability that can be permanent disability and are associated with premature death. Current treatments are able to effectively increase bone strength in osteoporotic patients but can not return bone strength to normal. Some new treatments can restore bone strength to some extent but these are limited by expense and safety concerns. We have discovered a pathway in the brain that reduces bone formation and by blocking this pathway we can achieve doubling of the amount of bone in key bone sites. This occurs due to a marked increase in the amount of new bone formed. In fact, genetic manipulation of this pathway was able to double the speed at which bone is made by the skeleton. Excitingly, these increases in bone were possible in adult mice, suggesting such changes could be potential therapy for human patients. However, in order to be able to harness this pathway we must understand what molecules within the brain are responsible for the signals that reach the bone. Our proposal aims to identify the nerve signalling molecule(s) and the receptor for these signals within the brain that initiates the increase in bone formation. This project ultimately aims to identify a target for new therapies that could cause this beneficial effect by administration of a simple treatment, preferably by mouth in adult humans.Read moreRead less
Preventing Adverse Effects Of Matrix Metalloproteinases In Diabetic Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$387,784.00
Summary
Treatment of diabetic foot ulcers presents a significant challenge to diabetic patients and the health care system. Despite concerted treatment, many ulcers do not heal and it is this failure to heal which eventually leads to deep-seated infection and amputation. For these reasons development of new therapeutic strategies to improve wound healing in diabetes is of critical importance. In this study we investigate the role of MMPs in particular MMP-9 in diabetic wounds and examine whether MMP inh ....Treatment of diabetic foot ulcers presents a significant challenge to diabetic patients and the health care system. Despite concerted treatment, many ulcers do not heal and it is this failure to heal which eventually leads to deep-seated infection and amputation. For these reasons development of new therapeutic strategies to improve wound healing in diabetes is of critical importance. In this study we investigate the role of MMPs in particular MMP-9 in diabetic wounds and examine whether MMP inhibition will improve wound healing in diabetes.Read moreRead less
The Effects Of Zoledronic Acid On Bone Architecture In Premenopausal Women With Breast Cancer Receiving Adjuvant Combined Ovarian Suppression And Aromatase Inhibitor Therapy: A Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
In premenopausal women, a new treatment method that reduces oestrogen levels to almost zero significantly reduces the risk of breast cancer recurrence. However, this is likely to cause substantial bone loss leading to fractures. Using a new imaging technique (HR-pQCT), the effects of profound oestrogen deprivation on bone structure in premenopausal women will be studied. The ability of zoledronic acid, a drug that reduces bone loss, to prevent these adverse bone effects will also be examined.