The Role Of Huntingtin Misfolding And Oligomerization In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$474,329.00
Summary
Mutations in the huntingtin gene cause Huntington's disease by making the gene product aggregate together into non-normal and different sized polymers. However, it is not understood how this process causes cells to die, largely because we don't understand how the abnormal forms accumulate in cells over time. We will examine where in cells the abnormal shapes accumulate and how they cause toxicity. This research will identify critically-needed therapeutic targets against Huntington's disease.
Computational Modelling To Understand Early-stage Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Rather than attempting to reverse neurodegeneration, therapeutic strategies must target the earliest possible stages of disease, when treatments have the potential to prevent or slow down pathological progression. The proposed project will employ computational modelling using functional MRI to deliver highly efficient and sensitive markers of Familial Alzheimer’s disease and Huntington’s disease progression to inform when in the progression of disease clinical trials should take place.
Longitudinal Transcriptome Profiles For People With Dementia
Funder
National Health and Medical Research Council
Funding Amount
$475,913.00
Summary
Over the past decade, less than half a percent of drugs trialled for Alzheimer Disease were found to be effective. This highlights the need for new drug targets. This Fellowship aims to study how genes express themselves over time, among people with very high risk of dementia (genetic form of Alzheimer Disease and Huntington Disease). By looking at gene expression in nerve tissue in the nose, fluid around the brain, and blood, I hope to better understand the disease mechanisms causing dementia.
Mapping Brain Network Interactions In Neurodegenerative Disorders Of The Subcortex
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Huntington’s disease, Parkinson’s disease, and Friedreich ataxia are debilitating and progressive neurodegenerative disorders that result from cell death within different components of a common brain system. Using magnetic resonance imaging and advanced statistical techniques, I will investigate functional and structural changes within this system, providing a clearer picture of the brain network changes that underlie the expression of these disorders.
A Study Addressing Motor, Cognitive And Attentional Deficits In Presymptomatic Gene Carriers For Huntington's Disease
Funder
National Health and Medical Research Council
Funding Amount
$180,330.00
Summary
Since the discovery of the Huntington's disease (HD) gene mutation there has been much controversy in the literature relating to whether there are any preclinical deficits in individuals who are gene positive for HD but who have not yet been clinically diagnosed with the disease. Our aim is to examine, over a three year period, the cognitive, attentional and motor performance of presymptomatic gene-positive, and negative, individuals on a wide variety of computerized experimental procedures, whi ....Since the discovery of the Huntington's disease (HD) gene mutation there has been much controversy in the literature relating to whether there are any preclinical deficits in individuals who are gene positive for HD but who have not yet been clinically diagnosed with the disease. Our aim is to examine, over a three year period, the cognitive, attentional and motor performance of presymptomatic gene-positive, and negative, individuals on a wide variety of computerized experimental procedures, which we have previously shown to be sensitive to deficits in individuals who have already been diagnosed with HD. If progressive behavioural changes in gene-positive individuals can be reliably documented to occur before the clinical symptoms of HD are evident, this would be of profound significance as it would allow a set of criteria to be established to assist in early detection of clinical onset of symptoms, and possibly permit use of newly-emerging therapies.Read moreRead less
Viewing The Cellular Responses In Huntington’s Disease Through An Aggreomics Framework
Funder
National Health and Medical Research Council
Funding Amount
$363,218.00
Summary
Huntington disease results from a mutation that causes the Htt protein to form abnormal toxic clusters in neurons that eventually leads to cell death. This project will develop and apply new technology to identify how the clustering process damages cells and will measure all the gene expression changes that occur during the clustering process. The project offers much potential for revealing new therapeutic targets to this incurable disease.
Therapeutic Targeting Of Complement C5a Receptors In HuntingtonÍs Disease
Funder
National Health and Medical Research Council
Funding Amount
$468,312.00
Summary
HuntingtonÍs disease is a genetic neurodegenerative condition leading to progressive cognitive and motor deficits and eventual death. This research aims to explore the role of immune and inflammatory pathways in the progression of disease in patients suffering HuntingtonÍs disease, as well as in an animal model of this condition. By exploring these immune and inflammatory pathways, we aim to identify novel therapeutic targets to treat HuntingtonÍs disease.
Huntington’s disease is a devastating neurological disorder, with no drugs currently available to cure or treat the underlying cause. Our recent laboratory work on a drug called PBT2 was the foundation of a encouraging clinical trail for this disease. Here, we propose to investigate a drug called Zn(DTSM) for this disease, which has similar properties to PBT2, but we expect will have a greater effect.