While there are numerous therapies for relapsing-remitting multiple sclerosis (MS), therapy for progressive MS remains elusive. This project will evaluate the effect of various therapies on the accumulation of irreversible disability in progressive MS. In addition, it will examine the effect of switching between therapies on MS activity. Finally, the project will indicate whether demographic and clinical information can be used as a predictor of individual patient response to MS therapies.
Training To Enhance Lower Limb Motor Control In Hemiplegic Cerebral Palsy.
Funder
National Health and Medical Research Council
Funding Amount
$107,204.00
Summary
Currently very few evidence based methods that can improve control in muscles affected by cerebral palsy (CP) exist. This project will investigate whether it is possible to increase strength and co-ordination in legs muscles affected by CP through targeted training. The project will also determine if non-invasive brain stimulation during training may enhance motor learning and if positive gains in strength and co-ordination might enhance the ability to do tasks like walking or climbing stairs.
Implementing Neuroprotective Strategies For Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$782,370.00
Summary
Fetal growth restriction (FGR) is a serious and common complication of pregnancy that is a principal cause of injury to the developing fetal brain. In turn, damage to the developing brain during pregnancy may cause cerebral palsy and other cognitive and behavioural deficits. This proposal builds on my work to date characterising the mechanisms that contribute to neuropathology in FGR infants, by implementing targeted strategies to protect or repair the FGR brain.
Injury to the developing brain, whether sustained during pregnancy or at birth, is the underlying cause of many cognitive and motor disabilities, including cerebral palsy. This project will identify the cellular pathways that cause developmental brain injury in preterm and term infants, and then administer umbilical cord blood stem cells at different timepoints to assess their efficacy at reducing brain injury. This project will inform treatment with cord blood stem cells in high risk infants.
Molecular Mechanisms Linking Proteinuria And Sodium Retention
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive pro ....The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive protein loss in the urine is primarily due to problems in the filtering units of the kidneys, rather than due to abnormalities in the reabsorption of protein in the kidney tubules. However, we consider that common abnormalities in the processes within the kidney tubules that regulate both the reabsorption of salt and the excretion of acid may result in concomitant high blood pressure and increased protein loss in the kidney. Thus the overall aim of the project is to investigate the interrelationship between protein reabsorption and catabolism and Na+ reabsorption in the human kidney tubule. The project uses the combined methods of cultured human kidney tubules, biochemical and molecular biology techniques which are unavailable in other laboratories in Australia (and internationally). This project will comprehensively characterise the mechanisms of protein uptake and salt reabsorption in human kidney tubule cells when exposed to both normal and high concentrations of protein. The exact nature of the interaction of protein uptake with salt reabsorption and hence high blood pressure will be determined. As both hypertension and persistent proteinuria are the most important predictors of tubulointerstitial pathology and progressive decline in renal function in almost all renal disease, the understanding of the precise interaction between these two factors is essential in the design of renoprotective therapies.Read moreRead less
MODIFICATION OF TUBULE CELL CYTOKINES REGULATING INTERSTITIAL INFLAMMATION IN CHRONIC PROTEINURIC RENAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$294,121.00
Summary
Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year 1500 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. One of the major reasons for progression of kidney failure is that kidney cells produce a complex network of inflammatory mediators (cytokines) which attract inflammatory cells into the suppo ....Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year 1500 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. One of the major reasons for progression of kidney failure is that kidney cells produce a complex network of inflammatory mediators (cytokines) which attract inflammatory cells into the supporting tissue of the kidney (the interstitium). Recently, drugs that inhibit these cytokines have been used in animal models of chronic kidney disease. Such treatment regimens have been at most only partially effective because they have been directed against only one cytokine, and because they have ignored the fact that the profile of cytokines varies with stage of disease. This project will use a rodent model (Adriamycin nephrosis) of human chronic kidney disease to define strategies for preventing interstitial inflammation using anti-cytokine therapy. Our laboratory has identified three cytokines which appear to play a pivotal role in the development of interstitial inflammation in Adriamycin nephrosis, and shown that their production varies with time. Knowledge of the time-dependent interactions among and regulation of these cytokines will be used to define optimal delivery of therapy directed against all three cytokines. As anti-cytokine therapy is already being trialled in other types of (non-kidney) disease in humans, the success of such a therapeutic approach to treating progressive kidney disease in this animal model will have important and immediate implications for the treatment of chronic kidney disease in humans.Read moreRead less
A Genomic Basis For Cerebral Palsy - Studies On A Large Australian Cohort
Funder
National Health and Medical Research Council
Funding Amount
$518,305.00
Summary
Cerebral Palsy (CP) is the commonest neurological disability in children, affecting 1 in every 500 children. This research will investigate genetic causes of CP by testing families with and without CP for a range of genetic alterations that change fetal protection to inflammation with resultant brain damage and CP. Research in to the causes of CP will allow prevention strategies to be developed, to ultimately reduce social and financial costs of CP for the patient, their family and the community ....Cerebral Palsy (CP) is the commonest neurological disability in children, affecting 1 in every 500 children. This research will investigate genetic causes of CP by testing families with and without CP for a range of genetic alterations that change fetal protection to inflammation with resultant brain damage and CP. Research in to the causes of CP will allow prevention strategies to be developed, to ultimately reduce social and financial costs of CP for the patient, their family and the community.Read moreRead less
A Model Of Current & Potential Palliative Care Constituency: Measuring Met & Unmet Needs
Funder
National Health and Medical Research Council
Funding Amount
$145,210.00
Summary
Although many health care providers believe palliative care should be offered to all Australians who need it, there is no population-based data to support this claim. This study will provide much needed population-based evidence by measuring the levels of met and unmet needs of people with active, progressive, advanced disease in the last 12 months of their lives. A model of current and potential palliative care constituency will be developed that will lead to improved access to palliative care ....Although many health care providers believe palliative care should be offered to all Australians who need it, there is no population-based data to support this claim. This study will provide much needed population-based evidence by measuring the levels of met and unmet needs of people with active, progressive, advanced disease in the last 12 months of their lives. A model of current and potential palliative care constituency will be developed that will lead to improved access to palliative care for people who do not traditionally access specialist palliative care services.Read moreRead less