Gene Profiling To Develop A Neuroprotective Strategy In A Large Animals Model Of Following Ischaemic Stroke.
Funder
National Health and Medical Research Council
Funding Amount
$359,897.00
Summary
Stroke affects 15 million people worldwide each year. At present, the diagnosis and treatment of stroke is not optimal. The use of gene profiling may provide us with information that could allow us to more accurately identify individuals at risk of stroke, predict stroke outcome and effectively treat stroke patients. In addition, by using a targeted approach to therapy we have the potential to reduce brain swelling and improve outcome following stroke with neuroprotective agents.
Insights Into The Acute Cerebral Lesion Of Childhood Diabetes And It's Neuropsychological Sequelae
Funder
National Health and Medical Research Council
Funding Amount
$416,000.00
Summary
Type 1 diabetes in childhood is a major cause of morbidity with an Australian prevalence of approximately 20 per 100,000 children under 15 years of age. The leading cause of death in type 1 diabetes in children and adolescents is diabetic ketoacidosis complicated by cerebral oedema (brain swelling), the origins of which remain unknown. This research is aimed at providing an insight into changes in the brain of children with diabetic ketoacidosis (DKA) and the relationship of these brain changes ....Type 1 diabetes in childhood is a major cause of morbidity with an Australian prevalence of approximately 20 per 100,000 children under 15 years of age. The leading cause of death in type 1 diabetes in children and adolescents is diabetic ketoacidosis complicated by cerebral oedema (brain swelling), the origins of which remain unknown. This research is aimed at providing an insight into changes in the brain of children with diabetic ketoacidosis (DKA) and the relationship of these brain changes to short and long term neuropsychological functioning. The major aim of this project is to provide an insight into brain changes of children with diabetic ketoacidosis (DKA) and the relationship of these brain changes to subseuqent brain function. This is a study where we will simply observe differences between newly diagnosed type 1 diabetic patients with no ktoacidosis, ketoacidosis or ketoacidosis with brain swelling over 6 months. We will measure brain function using various techniques includiung: magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electrophysiology (EEG) and neuropsychological tests. The significance of this project is that it will provide insight into the brain impairment of diabetic patients with and without DKA, and with brain swelling in the context of DKA. By further clarifying the nature of brain impairment we will provide early intervention strategies to improve psychological development of the young patients with diabetes. In addition to this we hope to better understand the origins of brain swelling during DKA and design treatment protocols that will prevent this devastating complication.Read moreRead less
An Open-label Extension Of A Randomised Clinical Trail Of Intravitreal Triamcinolone For Diabetic Macular Oedema
Funder
National Health and Medical Research Council
Funding Amount
$167,733.00
Summary
A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, ....A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, double masked clinical trial of intravitreal triamcinolone for refractory macular oedema in 2002. The 3 month results from this study provide the first scientific proof of principle that intravitreal triamcinolone reduces macular thickness and improves vision. The two year results will be available in March 2005, but confidential interim analysis of efficacy data in September 2004 suggested that the beneficial effect of triamcinolone treatment persisted. Thus it appears that treatment with intravitreal triamcinolone may be the most significant development for the prevention of blindness in people with diabetes since the introduction of laser treatment. It would also be a highly cost-effective intervention that could be administered by general ophthalmologists. The treatment cannot be recommended for routine use, however, until its long term efficacy and safety have been established. Since we already have a well studied group of patients who have received treatment for 2 years, we are in a unique position to extend the study in order to provide the long-term (5-year) safety and efficacy data that does not appear to be forthcoming from any other source. The results of this study will significantly improve knowledge of long-term outcomes of local high dose steroids for diabetic macular oedema, allowing the treatment to be used more rationally. Thus the study is very likely to directly reduce the risk of blindness in people with diabetes.Read moreRead less
Modulation Of Endothelial Junctions As Selective Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$911,387.00
Summary
We have developed a new drug (CD5-2) that targets the junctions of endothelial cells, the cell that lines all vessels. CD5-2 reduces oedema in diseases such as diabetic retinopathy and tumours. Thus it has potential as a new therapeutic in chronic inflammatory diseases where leaky blood vessels are central to the pathology. This grant will provide fundamental understanding of how CD5-2 induces such profound effects to alter the levels of oedema and alter inflammatory cell infiltrates in tissues.
Establishing A Model Of Occlusive Middle Cerebral Artery Stroke In The Sheep
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Stroke is the second leading cause of death and the highest cause of disability in adult Australians, however our lack of an animal model that correctly replicates the human condition has severely hindered our understanding and treatment of the disease. This research project aims to develop a model of stroke in the sheep using a surgical approach that future researchers may use and adapt to further explore the physiology of the disease and trial therapeutic techniques to treat stroke.
Improving Clinical Translation In Stroke: Targeting Cerebral Oedema In A Large Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$637,530.00
Summary
A common and life-threatening complication of stroke is brain swelling which is the leading cause of death within one week of stroke and a predictor of poor outcome. Current treatments for brain swelling are inadequate. We have developed a drug that blocks the action of the neuropeptide substance P, which is involved in the development of swelling. We will assess the efficacy of this treatment to reduce brain swelling and improve long-term outcome in a relevant pre-clinical model of stroke.
Blood-Spinal Cord Barrier Structure And Function In Syringomyelia
Funder
National Health and Medical Research Council
Funding Amount
$82,630.00
Summary
Syringomyelia is a disorder in which a fluid-filled cyst forms within the spinal cord. These cysts expand over time resulting in paralysis or even death. Syringomyelia occurs in association with spinal cord injury and a number of congenital conditions. In this project we aim to investigate the underlying cause of cyst formation, which is currently unknown. It is hoped that these studies will improve our understanding of cyst formation and facilitate development of better treatment strategies.
The aim of this project is to better understand the events that cause the onset of uveitis, a common cause of visual impairment and blindness in adults. Toll like receptors (TLR) are a new group of cell surface receptors tinflammatory mediators.hat are important in immune function and the immune system's ability to recognise and respond to to microbes by recognising signature molecules contained in microbes. The TLR system is the early warning system of immune defence and activation of the TLR s ....The aim of this project is to better understand the events that cause the onset of uveitis, a common cause of visual impairment and blindness in adults. Toll like receptors (TLR) are a new group of cell surface receptors tinflammatory mediators.hat are important in immune function and the immune system's ability to recognise and respond to to microbes by recognising signature molecules contained in microbes. The TLR system is the early warning system of immune defence and activation of the TLR system induces the generation of multiple mediators that initiate and perpetuate inflammation. There has been intense interest and research into this novel family of receptors and they have been shown to play an important role in human diseases such as inflammatory bowel disease and psoriasis. The role of TLRs in uveitis has not been studied. We hypothesise that TLRs play a central role linking certain bacteria and the induction of uveitis. TLR4, a member of the TLR family has been clearly identified as the key receptor for cell wall components of gram negative bacteria (a chemical called LPS). In vitro data shows that TLR4 stimulation by LPS causes the release of inflammatory mediators. This project is designed to study the expression of TLRs in the eye, factors that control their expression and the results of stimultaing TLRs with their target chemicals. Better understanding ofd the causes and mechanisms of uveitis will allow the development of more specific and effective treatments.Read moreRead less