The L-type Calcium Channel As A Reporter Of Successful Morpholino Oligomer Therapy In Treatment Of Duchenne Muscular Dystrophy Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$595,062.00
Summary
Duchenne Muscular Dystrophy is a fatal muscle wasting disorder. We have previously characterised how the heart fails in a mouse model of muscular dystrophy. We now have preliminary data demonstrating that treatment of mice with morpholino oligomers can rescue cardiac function. This project will fully characterise the effect of the treatment on heart function and optimise therapy regimes with the view to utilising the optimised protocol as a guideline in treating cardiomyopathy in Duchenne Muscul ....Duchenne Muscular Dystrophy is a fatal muscle wasting disorder. We have previously characterised how the heart fails in a mouse model of muscular dystrophy. We now have preliminary data demonstrating that treatment of mice with morpholino oligomers can rescue cardiac function. This project will fully characterise the effect of the treatment on heart function and optimise therapy regimes with the view to utilising the optimised protocol as a guideline in treating cardiomyopathy in Duchenne Muscular Dystrophy boys.Read moreRead less
Defining The Role Of Glycosylation In Basement Membrane Failure During Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$824,664.00
Summary
This project aims to utilize mutations within the zebrafish fkrp gene to understand the pathogenic basis of the human diseases associated with mutation of this gene which results in a spectrum of muscular dystrophies. By generating models of alleles that represent the range of phenotypes seen in humans we will have a directly translatable model system to human pathology.
Dysferlin And The Emergency Vesicle Fusion Of Membrane Repair
Funder
National Health and Medical Research Council
Funding Amount
$481,496.00
Summary
Membrane repair is a vital cell survival mechanism of all eukaryotic cells, using calcium-triggered vesicle fusion to ‘patch’ membrane ruptures. The muscular dystrophy protein dysferlin is a key mediator of membrane repair, although, exactly how dysferlin mends membranes has been unclear. We show that the calcium that floods through membrane tears, activates a group of enzymes called calpains, that specifically cleave dysferlin to release a specialist vesicle-fusion module for membrane repair.
Modelling Laminin Mediated Adhesion And Congenital Muscular Dystrophy In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Congenital Muscular Dystrophy (CMD) is a muscle wasting conditions arising from mutations in the Lamina alpha 2 gene (lama2) gene. We have established zebrafish as a model system in which to determine the mechanistic basis of CMD pathology. We have isolated mutations in the zebrafish Lama2 gene and have determined that Lama2-deficient zebrafish accurately model the human condition. We aim to use the advantages of the zebrafish system to model treatments for muscular dystrophy
Evaluation And Design Of Therapeutic Strategies Utilizing Zebrafish Genetic Models Of Duchenne Muscular Dystrophy.
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Duchenne and Becker Muscular Dystrophy (MD) are allelic muscle wasting conditions arising from mutations in the dystrophin (DMD) gene. We have established zebrafish as a model system in which to determine the mechanistic basis of DMD pathology. We have isolated mutations in the zebrafish dystrophin gene and have determined that Dystrophin-deficient zebrafish accurately model the human condition. We aim to use the advantages of the zebrafish system to model treatments for muscular dystrophy.
Advancing Glycine To The Clinic For Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$248,978.00
Summary
We have identified the therapeutic potential of the amino acid glycine for Duchenne muscular dystrophy (DMD), the most common and severe of the muscular dystrophies. To facilitate rapid translation to the clinic, this proposal will; 1) examine the effect of glycine on lifespan and quality of life in mouse models of DMD; 2) determine glycine’s mode of action; and 3) investigate whether these effects represent further benefits to those currently used gold standard treatments.
Modeling Emery-Dreifuss Muscular Dystrophy In Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$460,190.00
Summary
Emery-Dreifuss muscular dystrophy (EDMD) is a muscle degenerative disease characterised by specific muscle degeneration. Human genetic studies have identified specific genes that are mutated in patients with EDMD. We have generated zebrafish models of the most common forms of EDMD and propose to use these models to determine how mutations in these genes contributes to a lack of muscle integrity in this muscular dystrophy.
Preclinical Testing Of 3 Cysteine-related Drugs For Reducing Dystropathology In The Mdx Mouse Model Of Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$378,564.00
Summary
Duchenne muscular dystrophy (DMD) is devastating disease that affects young boys. We propose testing 3 cysteine related drugs which show promise in ameliorating the severity of the disease. The drugs are of particular interest because they are relatively inexpensive, can be taken orally, have few side effects and are already approved for human use. These drugs will tested in an animal model of DMD to test their efficacy.
Characterisation Of The Pathogenesis Of FHL1 Myopathies
Funder
National Health and Medical Research Council
Funding Amount
$748,652.00
Summary
Skeletal muscle is the most abundant tissue in the body and dynamically capable of responding to many environmental stresses. A key cellular process that has developed in muscle to facilitate adaptive responses is autophagy, a mechanism that facilitates the degradation and recycling of cellular debris. Defects in autophagy cause muscle disease. In this study we will identify a novel gene that regulates autophagy and will investigate how mutations in this gene cause muscle disease.
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.