Orexin/Hypocretin Receptors In Self-Administration And Stress-Induced Reinstatement Of Ethanol Seeking
Funder
National Health and Medical Research Council
Funding Amount
$538,221.00
Summary
Orexin receptors are novel therapeutic targets implicated in alcohol use disorders. There is little known about how orexin receptors drive ethanol consumption and stress-induced reinstatement. This project provides a unique opportunity to determine the mechanism of action of orexin receptors in alcohol use disorders and devise novel therapeutic strategies to treat alcohol use disorders.
Targeting Autophagy To Improve Protein Metabolism In ALS
Funder
National Health and Medical Research Council
Funding Amount
$586,001.00
Summary
One common feature of MND is the accumulation of protein deposits inside nerve cells which leads to their death. We have identified a potent drug which enhances autophagy, a protective process which breaks down protein deposits inside cells. We have shown that this autophagy enhancer efficiently clears protein deposits linked to MND in the Petri dish. We propose to treat MND mice with this autophagy enhancer and predict that it will slow disease signs, preserve lifespan and protect nerve cells.
The Role Of Excitotoxicity In Mediating Distal Axonal Degneration In ALS
Funder
National Health and Medical Research Council
Funding Amount
$392,952.00
Summary
Amyotrophic lateral sclerosis (ALS), the major cause of motor neuron disease, is a devastating diseasse for which there is no cure. There have been significant advances in understanding the pathology of ALS yet we still don’t know what causes the dying back of spinal motor neurons. We have new evidence that suggests that ALS may, in part, be caused by excitotoxcity - or over stimulation - of neurons in the spinal cord. We will follow this lead using a range of cutting edge experimental models.
Pathophysiology, Site Of Disease Onset And Mechanisms Of Spread In Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$704,270.00
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal disease of the human motor system resulting in progressive paralysis of voluntary muscles and death within 5 years of symptom onset. A key unresolved issue in the understanding of where ALS starts and what factors drive the disease. This project will utilise sophisticated techniques to determine the site of onset, factors controlling disease spread and ultimately identify treatment targets that could slow down or even stop disease progression.
Using Trios To Find The Cause Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$636,544.00
Summary
The cause of motor neuron disease (ALS) remains unknown. Usually only one member of a family is affected by ALS. Why parents are unaffected by the disease is unexplained. This may be because a genetic abnormality is present in the ALS patient but not in the parents. We have therefore collected DNA from ALS patients with their normal parents to look for newly-arising genetic changes in ALS patients. These findings could enable future gene therapy for these patients.
Gene Discovery In Motor Neuron Disease Through Systems Genomics
Funder
National Health and Medical Research Council
Funding Amount
$938,932.00
Summary
Motor neuron disease (MND) is an adult-onset, rapidly progressive neurodegenerative disorder that leads to paralysis and death, typically within 2 to 5 years of first symptoms. More than 85% of cases do not harbour known MND mutations. This proposal exploits genome-wide genetic and epigenetic profiling methods and leverages across multiple existing genomic resources to discover genes and functional pathways that contribute to MND pathogenesis and progression.
Investigating The Propagation Of Protein Aggregation In Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$406,217.00
Summary
Motor Neurone Disease is a rapidly progressive disease that attacks neurones responsible for controlling voluntary muscles, leading invariably to death. Currently there is no effective treatment. Recent work in humans suggests that degeneration begins focally and spreads through the three dimensional anatomy of the nervous system. This project will address the important question of how the toxicity is spread amongst adjacent neurones by characterising the propagation of protein aggregates.
Understanding The Early Disease Mechanisms Of Motor Neuron Disease And Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$692,487.00
Summary
Motor neuron disease (MND) and frontotemporal dementia (FTD) are incurable, fatal neurodegenerative diseases. MND and FTD patients have similar brain and spinal cord pathology, but the causes of disease remain unclear. Using new genetically modified mice that for the first time recapitulate key features of the human diseases, this project will define the biochemical processes that contribute to disease onset and progression and will test potential disease-modifying therapeutics.
The Role Of Mutant CYLD In Frontotemporal Dementia And Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$963,216.00
Summary
We have identified a new gene that when mutated causes dementia and motor neuron disease (MND), diseases that are currently incurable. This project will examine how this mutated gene affects cell functions to cause nerve cell death, using cutting-edge cell and mouse models of disease, and find out whether people who have more common variants of this gene are at greater risk of developing dementia or MND. This knowledge is crucial for diagnosing and developing therapies for these disorders.
The Role Of Mutant Cyclin F In Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$1,012,933.00
Summary
Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease, MND) is characterised by rapid paralysis leading to death within 2 to 5 years of onset. There are no effective diagnostic tests or treatments. Confusion remains around the primary cause of paralysis. We recently discovered ALS gene mutations that disrupt normal nerve function, a process known as abnormal protostasis. This gives us a unique opportunity to unlock the primary cause of paralysis and develop animal models of ALS