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What Contributes To Regional Vulnerability In Neurodegenerative Diseases? A Study Of Familial Cases.
Funder
National Health and Medical Research Council
Funding Amount
$456,655.00
Summary
Unfortunately, as many people live longer, more and more are afflicted by degenerative changes that affect their brain. These neurodegenerative diseases are usually relentlessly progressive and with time render patients incapable of many normal functions. For some families with certain genetic defects, these diseases occur aggressively and early. We would like to study the brains of patients from these families because in most cases the proteins affected by the gene defect have been identified. ....Unfortunately, as many people live longer, more and more are afflicted by degenerative changes that affect their brain. These neurodegenerative diseases are usually relentlessly progressive and with time render patients incapable of many normal functions. For some families with certain genetic defects, these diseases occur aggressively and early. We would like to study the brains of patients from these families because in most cases the proteins affected by the gene defect have been identified. However, despite knowing this important information, the reasons for the death of brain cells are still not understood. This project will provide important new information on which brain cells died in these patients and on the relationship between such cell death and any cellular protein changes. By comparing patients with different genetic defects we will be able to identify the main cellular mechanisms underlying these degenerative changes. This information is essential for the rational design of further experiments aimed at reducing the suffering of all patients with neurodegenerative diseases or at eliminating these diseases altogether.Read moreRead less
Assessment Of The Effectiveness Of Australian Models Of Palliative Care Delivery In Four Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
This study will be conducted in three Australian states (Queensland, Victoria and West Australia), to assess the effectiveness of existing palliative care service delivery to people with motor neurone disease, multiple sclerosis, Huntington’s disease or Parkinson’s disease, and to their families. In phase I, interviews will be conducted with people who have these diseases, their families, and health professionals to discover the needs for palliative care services. In phase II, a survey will dete ....This study will be conducted in three Australian states (Queensland, Victoria and West Australia), to assess the effectiveness of existing palliative care service delivery to people with motor neurone disease, multiple sclerosis, Huntington’s disease or Parkinson’s disease, and to their families. In phase I, interviews will be conducted with people who have these diseases, their families, and health professionals to discover the needs for palliative care services. In phase II, a survey will determine the extent to which these needs are met. The findings will be used to recommend improved palliative care delivery models.Read moreRead less
Clinical Phenotypes And Novel Neurophysiological And Immunological Biomarkers In Inflammatory Neuropathy And Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$83,970.00
Summary
The aim of this project is to define subgroups of inflammatory neuropathies by correlating clinical phenotypes with immunological & neurophysiological profiles. The identification of specific autoantibody markers in patients with inflammatory neuropathies will aid in diagnosis &differentiation from motor neurodegenerative disorders. Identification of prognostic novel biomarkers that predict response to immunotherapy will be invaluable in the clinical setting & allow for better treatment planning
Parkinson's disease is a progressive, disabling, age-associated neurological disorder with no known cure. Several genes have been identified as causing Parkinson's disease, although mutations in leucine-rich repeat kinase2 (LRRK2) are by far the most common. The studies we propose will identify the cellular proteins that interact with LRRK2 to cause Parkinson's disease. These proteins may be amenable to future therapeutic manipulation.
How Do Small Extracellular Vesicles Contribute To The Development Of Prion Disease
Funder
National Health and Medical Research Council
Funding Amount
$563,897.00
Summary
Prion diseases are transmissible neurodegenerative disorders associated with the misfolding of the prion protein. This proposal will investigate how cells release the infectious agent responsible for prion diseases in small nanovesicles known as exosomes. We will characterise the novel processed forms of the proteins involved in these two neurodegenerative diseases within the exosomes and investigate whether the genetic content of exosomes has diagnostic potential.
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.
Cellular Pathogenesis Of Key Proteins Involved In Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$312,730.00
Summary
Prion proteins are involved in neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and Bovine Spongiform Encephalopathy (BSE). The aim of this research proposal is to investigate factors which can change the prion protein from a normal, benign, form into an abnormal shape which can cause disease. The outcomes of this work will provide further insight into the role of prion proteins in these diseases and also for other neurodegenerative disorders such as Alzheimer's disease.
Nix Mediated Mitophagy: A New Therapeutic Approach To Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,428.00
Summary
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder in the world. A key problem in PD is that affected neurons lose energy and then die. We have discovered that by recycling mitochondria (the parts of the cell that produce energy), we can protect neurons from dying and restore function. This project will determine whether mitochondrial recycling mediated by Nix can restore energy and prevent neuronal loss. This would represent a new therapeutic approach to treat PD.
Molecular Basis Of Mitochondrial Complex I Deficiency, The Most Common Energy Generation Disorder
Funder
National Health and Medical Research Council
Funding Amount
$515,750.00
Summary
Oxygen is needed by every cell in the body to burn fuels (ie sugar, fat and protein) in small power plants inside each cell called mitochondria. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause a range of degenerative diseases later in life, particularly affecting brain, muscle and heart. In most cases we do not have any effective treatments. A major problem in understandin ....Oxygen is needed by every cell in the body to burn fuels (ie sugar, fat and protein) in small power plants inside each cell called mitochondria. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others cause a range of degenerative diseases later in life, particularly affecting brain, muscle and heart. In most cases we do not have any effective treatments. A major problem in understanding mitochondrial energy generation disorders is that the genetic causes are incredibly diverse. So far more than 20 genes have been shown to cause mitochondrial disorders, and it is likely that over one hundred more genes remain to be discovered. In addition to the regular genes that cause these and other genetic disorders, mitochondria are unique in carrying 37 extra genes located in a different part of the cell away from the rest of the human genome, and inherited only from the mother. This grant focuses on the most common energy generation disorder, known as Complex I deficiency. Complex I requires 43 separate components to be assembled together in order to work properly, but mutations in the 43 genes encoding these components are not present in most patients. We believe that the most common problems will be in genes involved in assembling the 43 components rather than in the components themselves. We will use a number of methods to pinpoint where in the genome the causative genes are located and then home in on the exact changes in the genes that cause disease. Identifying these genes will allow us to improve future diagnosis and prevention of mitochondrial disease. Understanding the basic biology may also allow us to develop new methods of treatment. Recent studies suggest that milder mitochondrial problems also contribute to a range of more common diseases such as diabetes and Parkinson disease, so any new treatments could potentially have wide application.Read moreRead less