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
Viral Therapy For Skeletal Muscle Alpha-actin Disease And Discovery Of Novel Neuromuscular Disease Genes And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$324,028.00
Summary
This research project is the next logical step towards treating patients with skeletal muscle actin disease - using viral delivery of normal actin genes in animal models of actin disease. Another arm of this project is to investigate the genetics and mechanisms causing two very different groups of muscle disorders in the Australian population: devastating muscle weakness in the foetal akinesias and enhanced muscle strength and bulk in individuals with strongman syndromes.
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.
Nemaline myopathy is a neuromuscular condition characterised by muscle weakness, low muscle tone and the finding of nemaline bodies or rods on muscle biopsy. This study encompasses a natural history study of nemaline myopathy, genetic diagnosis and gene discovery using new methods of genetic testing, characterisation of a new disease gene for this condition, and reviewing patient experience with tyrosine, a medication commonly used in patients with nemaline myopathy.
Pathophysiology Of ALS: Evidence To Support The Dying Foward Hypothesis
Funder
National Health and Medical Research Council
Funding Amount
$49,471.00
Summary
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive, uniformly fatal, neurodegenerative disorder with peak age of onset for the common sporadic variant of the disease being in the middle productive period of 50-60 years. The current research project aims at clarifying the site of onset of disease within the motor system, specifically, the primacy of the corticomotorneuron in pathogenesis. This knowledge would be valuable in targeting interventions which modify disease progression.
Targeting Calcineurin For Improving Muscle Regeneration In Skeletal Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
Muscular dystrophy is a term that covers a diverse group of inherited disorders characterised by progressive muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most severe form, caused by a lack of a protein called dystrophin, which renders muscles fragile, susceptible to damage, and with a compromised ability to regenerate or repair after injury. The disease progresses to all muscles and DMD patients are dependent on a wheelchair before their early teens and die in their twen ....Muscular dystrophy is a term that covers a diverse group of inherited disorders characterised by progressive muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most severe form, caused by a lack of a protein called dystrophin, which renders muscles fragile, susceptible to damage, and with a compromised ability to regenerate or repair after injury. The disease progresses to all muscles and DMD patients are dependent on a wheelchair before their early teens and die in their twenties. There is a profound need for treatments that can ameliorate the dystrophic condition and improve patient quality of life. Restoring or increasing a muscle's capacity to regenerate would help improve muscle function. We have convincing evidence that the calcineurin signal transduction pathway is important for successful muscle regeneration in mice with muscular dystrophy. There is growing excitement worldwide that stimulating calcineurin could attenuate the dystrophic pathology, however, little is known about the role of calcineurin signalling in human muscle disease. Our goals are to investigate the role of calcineurin signalling in muscular dystrophy and to examine its therapeutic potential for enhancing muscle regeneration. Our aim is to better understand the mechanisms controlling calcineurin signalling in muscles of dystrophic mice and in muscles of patients with DMD. A comprehensive series of physiological, molecular, biochemical, and immunohistochemical experiments will be performed to rigorously test our research aim. Understanding the role of the calcineurin pathway in muscle regeneration is important for the development of novel therapeutic strategies to delay the onset or slow the progression of muscle wasting and weakness. The findings will have broad clinical application for our understanding of muscular dystrophy with relevance to other conditions including ageing, AIDS, burns, cancer cachexia, and disuse atrophy, where muscle wasting occurs.Read moreRead less
New tools to activate and silence neural circuits. Many neurological disorders occur as a result of neuron cell death that is initiated by excessive levels of excitatory activity in central nervous system neurons. This project will develop and validate a new treatment for these disorders that involves silencing excessive neuronal activity using a safe, commonly prescribed drug.
Protein Disulphide Isomerase And Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$307,524.00
Summary
Motor Neuron Disease (MND) patients currently face a bleak future. In the common global form of disease, the average length of survival after diagnosis is 31 months. Current therapies have at best a modest effect on the course of the disease with little or no benefit in terms of overall patient survival. We have new evidence that a protein called PDI can prevent the motor neuron cells from dying in MND and hence this may be a novel therapeutic target for both sporadic and familial forms of MND.
Discovery Early Career Researcher Award - Grant ID: DE120102961
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The role of the unfolded protein response in tau neurobiology and pathology. The main role of the protein tau is the stabilisation of the scaffolding of cells. In a group of dementias, tau forms abnormal clumps within the cells of the brain causing them to die. This project will investigate the cellular processes involved in normally preventing tau proteins from clumping and their role in the development of the abnormal tau clumps.