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Postsynaptic Signalling Systems That Sustain The Nerve-muscle Synapse
Funder
National Health and Medical Research Council
Funding Amount
$598,041.00
Summary
Neuromuscular junctions (NMJ) are the synapses through which motor nerves control our voluntary muscle cells. This project will investigate the molecular signalling system between nerve and muscle that helps maintain healthy NMJs. Normal ageing involves a progressive decline in muscle strength, often leading to loss of independence in the elderly. We will use a mouse model to test whether a breakdown of the NMJ signalling system contributes to the loss of strength in old age.
Characterisation Of A Novel Human Neuromuscular Disease Associated With Deficiency Of The Syntrophins And Dystrobrevin.
Funder
National Health and Medical Research Council
Funding Amount
$284,069.00
Summary
The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affec ....The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affected babies are never able to breathe adequately, and die during the first weeks of life. No specific treatment is currently available. Until recently the underlying gene and protein abnormalities resulting in the majority of cases of muscular dystrophy were unknown and hence definitive diagnosis and prenatal diagnosis was not possible. We have recently identified deficiency of a group of muscle proteins, the syntrophins and dystrobrevin, in 15 children with severe weakness, in whom the cause was previously unknown. This group of patients represent the first examples of a novel neuromuscular disorder. We will now identify the disease-causing genetic mutations in these patients and determine how abnormalities in these muscle proteins lead to muscle weakness and degeneration. This research will have immediate application to clinical practice as we will be able to give the childrens' families accurate information about the risk to future offspring and offer prenatal diagnosis. In addition, it will provide new and important information concerning the normal function of human skeletal muscle, which can be used to develop therapies for affected patients.Read moreRead less
Pathogenic Mechanisms In Inflammatory Demyelinating Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$378,750.00
Summary
The causes and disease mechanisms of inflammatory neuropathy remain mostly unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive, non-specific in action, beyond the means of the worlds most populous nations and a considerable burden to health resources in developed nations. These studies aim to understand better the mechanism of disease production so that better and more affordable therapy can be developed. In our current g ....The causes and disease mechanisms of inflammatory neuropathy remain mostly unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive, non-specific in action, beyond the means of the worlds most populous nations and a considerable burden to health resources in developed nations. These studies aim to understand better the mechanism of disease production so that better and more affordable therapy can be developed. In our current grant we have made a most important breakthrough - which is that antibodies to a major structural protein of the myelin sheath are responsible for disease production in one subgroup of patients. We plan to search for other antigenic targets in other patient groups and to see whether we can regulate the disease by new mechanisms which would be cheaper and more effective.Read moreRead less
The Role Of Antibody In Inflammatory Demyelinating Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$218,566.00
Summary
The causes and disease mechanism of inflammatory neuropathy remain unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive and non specific in action and beyond the means of the worlds most populous nations. These studies plan to illuminate the mechanism of disease production so that better and more affordable therapy can be developed. We have shown that antibodies which cause nerve damage are present in patients serum. Antib ....The causes and disease mechanism of inflammatory neuropathy remain unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive and non specific in action and beyond the means of the worlds most populous nations. These studies plan to illuminate the mechanism of disease production so that better and more affordable therapy can be developed. We have shown that antibodies which cause nerve damage are present in patients serum. Antibodies bind to specific target molecules and our work is close to identifying that target on nerve. We also plan to study how antibody leaks into nerve. This knowledge should allow more specific and effective treatment to be developed.Read moreRead less
Prediction of epilepsy seizure onset using nonlinear analysis of EEG recordings. This project will develop the theory and algorithms for reliable and robust prediction of the onset of epileptic seizures and the characterisation of epileptic seizures based on EEG data. Our interdisciplinary team consists of neuroscientists and systems engineers supported with clinicians and software developers. The team will develop the theory and design, implement and evaluate decision support software that is a ....Prediction of epilepsy seizure onset using nonlinear analysis of EEG recordings. This project will develop the theory and algorithms for reliable and robust prediction of the onset of epileptic seizures and the characterisation of epileptic seizures based on EEG data. Our interdisciplinary team consists of neuroscientists and systems engineers supported with clinicians and software developers. The team will develop the theory and design, implement and evaluate decision support software that is able to interpret eeg data and present epilepsy relevant information to clinicians and patients. Our methods are based on statistical signal processing, nonlinear dynamics (bifurcation and time-series methods) and systems engineering (system identification, adaptive methods).Read moreRead less
Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS rese ....Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS research including epidemiology, immunology and neurobiology. Collaboration of 8 major Australian institutions is also important for this project and future studies. The team will have access to a new national MS GeneBank (platform) with samples from 2240 patients that should generate findings important to world-wide MS genetic knowledge.Read moreRead less
The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themse ....The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themselves and information that could help in the development of new and more effective drugs, and biomarkers to assist in the prediction of prognosis. Such advances would decrease the economic impact of these diseases and improve quality of life for those affected.Read moreRead less