The Neuromuscular And Biomechanical Gait Risk Factors For Progression Of Hip Ostoearthritis.
Funder
National Health and Medical Research Council
Funding Amount
$91,367.00
Summary
Hip osteoarthritis (OA) is a common condition in older adults and it is often associated with pain, stiffness and functional limitations particularly in walking. There is no cure for hip OA and the end result is often a total hip replacement. Knowledge of neuromuscular and biomechanical characteristics of hip OA during walking and any relationships to disease progression will provide a better understanding of risk factors for progression of hip OA. This knowledge may guide future hip OA manageme ....Hip osteoarthritis (OA) is a common condition in older adults and it is often associated with pain, stiffness and functional limitations particularly in walking. There is no cure for hip OA and the end result is often a total hip replacement. Knowledge of neuromuscular and biomechanical characteristics of hip OA during walking and any relationships to disease progression will provide a better understanding of risk factors for progression of hip OA. This knowledge may guide future hip OA management plans to slow the progression of the disease.Read moreRead less
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
Molecular Pathology Of Collagen VI-related Muscular Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$574,500.00
Summary
The inherited muscular dystrophies, characterised by progressive muscle weakness and wasting, are a significant cause of physical disability. Muscle cells are anchored into the surrounding tissue by a chain of interacting proteins. Proteins inside the cell link to cell surface proteins, which in turn link to extracellular matrix proteins. If any one of the links is broken by a mutation, the connection is lost and muscle disease results. Most studies to date have focused on the role of intracellu ....The inherited muscular dystrophies, characterised by progressive muscle weakness and wasting, are a significant cause of physical disability. Muscle cells are anchored into the surrounding tissue by a chain of interacting proteins. Proteins inside the cell link to cell surface proteins, which in turn link to extracellular matrix proteins. If any one of the links is broken by a mutation, the connection is lost and muscle disease results. Most studies to date have focused on the role of intracellular and cell surface proteins, and relatively little attention has been paid to the extracellular matrix proteins. Mutations in the extracellular matrix protein collagen VI have been found in patients with Bethlem myopathy and Ullrich muscular dystrophy. These mutations tell us that collagen VI plays a critical role in muscle but we don't know how the mutations break the link between the cell and the matrix or why they cause a muscle disease. We will look for collagen VI mutations in our group of new Bethlem myopathy and Ullrich patients, and perform detailed studies on the effect of the mutations on collagen VI production, structure and function. These studies will allow us to provide accurate diagnosis and genetic counselling for affected individuals and begin to tell us how the mutations break the cell-matrix link. Mutations in other extracellular matrix proteins that interact with collagen VI are also likely to cause muscular dystrophies. One of these proteins is biglycan. We know from studies in mice that when biglycan is missing the mice have muscular dystrophy, so it is likely that some human muscular dystrophy patients have biglycan mutations. We will look for biglycan mutations in patients with muscular dystrophies and perform detailed studies to try to understand the effect of the mutations on the biglycan protein. This application brings together two groups with complementary expertise, to further our understanding of the basis of muscular dystrophies.Read moreRead less
Identifying Disease Genes For Neurogenetic Disorders Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$2,523,023.00
Summary
This project aims to identify novel disease genes, in other words, find genes, which have not previously been shown to cause human diseases when they are mutated. The collaborating laboratories on the project in Perth, Sydney, Melbourne and Boston, USA have a successful history in working together in finding human disease genes, harnessing, in the last few years, the now readily available power of next generation DNA sequencing to accelerate disease gene discovery.
An integrated platform built on efficient informatics concepts already implemented in international research infrastructures for large-scale data management, providing access to federated databases/registries, biobank catalogues, harmonised - omics profiles, and bioinformatics tools. Patient data types will be linked via a unique identifier “RD-ID” developed jointly with the US NIH. RD-Connect is a primary enabler for IRDiRC funded research to improve treatment and management of rare diseases
Role Of Synaptogenesis In Developmental Motoneuron Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$361,650.00
Summary
Naturally occurring cell death is an important and necessary event that shapes the developing embryo. It occurs in all organs of the developing body. In the nervous system about 50% of all neurons die at a time when they are making contact with one another or with their target organs. The underlying mechanisms that drive programmed neuronal cell death are not known. One possibility is that the formation of neuronal contacts (synapses) with other neurons and target cells determines the fate of a ....Naturally occurring cell death is an important and necessary event that shapes the developing embryo. It occurs in all organs of the developing body. In the nervous system about 50% of all neurons die at a time when they are making contact with one another or with their target organs. The underlying mechanisms that drive programmed neuronal cell death are not known. One possibility is that the formation of neuronal contacts (synapses) with other neurons and target cells determines the fate of a neuron. The connections of motor neurons with muscle during this period of developmental neuronal cell death is the best model to examine this phenomenon. In this grant we are in an exciting position to be able to address what causes neuronal cell death, as we have a number of mice that lack key molecules needed for the formation of specializations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motor neurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motor neurons' fate is determined during the period of programmed cell death. The outcomes of this research will enable us to understand how the nervous system is shaped during development and will increase our knowledge about the basis of adult neurodegenerative diseases. For example, the pathology of Alzheimer's is characterised by a breakdown in neuronal connections that ultimately result in neuronal death and a loss of thought processes (cognition).Read moreRead less
Lung Volume Recruitment In Neuromuscular Disease: Can Breath-stacking Improve Lung Function, Respiratory Symptoms And Quality Of Life In People With Neuromuscular Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$108,845.00
Summary
Difficulty taking deep breaths or coughing are two of the breathing complications people with a neuromuscular disease can face. Lung volume recruitment, also known as breath-stacking, is a simple and inexpensive therapy that may help. This research will look at the short and medium-term effects of breath-stacking exercises on the breathing system. If lung volume, chest stiffness and cough effectiveness improve then symptoms, quality of life and potentially survival are likely to be better.
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