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Neurodegenerative and neuromuscular diseases are difficult to diagnose and even more difficult to treat. They affect the elderly and children, usually at very early age, and often lead to premature death or chronic debilitation – they are usually incurable and 30-80% of patients remain undiagnosed. This program will identify new disease genes, establish routine diagnostics using cutting edge tools, identify novel and validate known biomarkers and develop novel treatment strategies.
Dementia is the third leading cause of death in Australia and the single greatest cause of disability in the elderly. Current therapies for Alzheimer’s disease (AD), the most common form of dementia, are inadequate and fundamentally new treatment approaches are required. The aim of this proposal is to develop novel drug candidates for the treatment and prevention of AD and other neurodegenerative disorders by targeting a class of cell-surface receptors called G protein-coupled receptors (GPCRs).
Alzheimer’s disease (AD), is the most common form of dementia, accounting for between 50-70% of all cases. There is general agreement that current treatments for AD/dementia are inadequate so new treatment strategies are desperately needed. I am addressing these challenges by developing new technologies to generate next generation treatments for AD.
Implications Of Retinal Neurodegeneration In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$602,213.00
Summary
Recent research has shown that “early signs” of Alzheimer ’s disease (AD) can be detected in the eyes. My research focus is to determine which particular changes in the retina are associated with AD. I will also investigate if blocking the production of beta amyloids (proteins produced in AD) in the eye will indeed help reduce their load in the brain and hence delay the onset of AD. Results from this research maybe used for early diagnosis and future medicinal studies that target the eye in AD.
Neuroprotective Functions Of Autophagy Regulators In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
The accumulation of the beta amyloid protein has a central role in AD and enhancing its removal improves memory loss in animal AD models. This project builds on my recent finding of regulators of a cell housekeeping system, “autophagy” which accelerate removal of beta amyloid in cells. This study will advance knowledge into the protective functions of the autophagy regulators in reducing AD symptoms. Findings from this work might provide the basis for developing effective anti-AD therapeutics.
The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
New Nanoparticle Strategies For Efficient Delivery And Controlled Release Into The Brain
Funder
National Health and Medical Research Council
Funding Amount
$571,633.00
Summary
A key challenge for treating neurodegenerative diseases is delivery of drugs across the blood–brain barrier (BBB). This project will develop advanced BBB “nanoshuttles” based upon systematic investigation of BBB penetration mechanisms and near-infrared drug controlled release strategy. These delivery systems may facilitate diagnosis of brain diseases and on-demand release of drug cargos to diseased cells in the brain, offering the potential of a brand new localised therapy for brain diseases.
Optimising Exercise Prescription For Brain Health In Older Adults At Risk Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$594,123.00
Summary
To reduce dementia burdens in the community, cost effective and targeted early regenerative strategies are critical. Engaging in frequent aerobic exercise is one strategy that can delay the onset and slow the progression of dementia. However, prescription is limited by an incomplete understanding of how exercise positively influences brain health. Here I will investigate the influence of current exercise levels, intensity and exercise environment on brain health in adults at risk of dementia.
Development And Epilepsy - Strategies For Innovative Research To Improve Diagnosis, Prevention And Treatment In Children With Difficult To Treat Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$456,083.00
Summary
By deciphering pathophysiological mechanisms in epileptogenic developmental disorders and developing mechanism-related, and advanced therapeutic strategies, we expect to discover novel genes and related molecular pathways that are involved in epilepsy and similar disorders. DESIRE will also help preventing the development of the disease after potentially epileptogenic brain insults.
Investigation Of Zinc Dyshomeostasis Associated With Aging And Dementia-related Disorders Using Novel Nanodiamond-based Markers
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
This project will illuminate the fundamental brain changes that lead to age-related cognitive decline by means of newly developed biamarker based on fluorescent nanodiamonds. The expected outcome of this work will be a unique approach to elucidate the source of cognitive decline that will fill a significant unmet need within the community.