Manipulating Store-operated Ca2+ Entry To Improve Muscle Function In Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$516,163.00
Summary
Muscle function is regulated in a complex manner by calcium and is impaired in Duchenne muscular dystrophy (DMD). Changes in calcium regulation will be investigated in DMD patients and in an animal model using a novel approach. We will use a combination of novel experimental approaches to manipulate muscles in dystrophic mice and test for improvement in function. Results will determine the viability of a potential treatment.
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
Pathways To Treatment In Blinding Genetic Retinal Eye Diseases
Funder
National Health and Medical Research Council
Funding Amount
$556,956.00
Summary
Blinding eye diseases with genetic contributing factors affecting the retina or light-sensing part of the eye, damage the vision of millions of people worldwide. The vision impairment is irreversible, untreatable, and worsens with age. In this project, we will use technological breakthroughs in genome correction and sequencing, in combination with stem cell and mouse model applications, to develop pathways to treatment of these currently incurable diseases.
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.
Self-destructing CRISPR-constructs For Targeted Genome Editing In The Retina.
Funder
National Health and Medical Research Council
Funding Amount
$679,926.00
Summary
Despite the identification of specific mutations causing many inherited retinal dystrophies, all of these conditions are currently untreatable. We have established gene-editing techniques and have developed a novel mouse model, which will serve as a robust platform for testing different techniques of gene editing in the retina. No other group in the world is known to be using this platform for gene editing and our work will expedite the clinical translation of this technology.
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.