Targeting The Oncoprotein MDMX As A Novel Treatment For Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$561,672.00
Summary
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCas unable to respond to current therapies have the worst outcomes. We propose a novel strategy to treat these cancers, based on our new findings. Our two protein targets are: (1) MDMX, that we found drives BrCa with its partner, (2) mutant p53, which causes cancer spread. We plan to directly target these drivers of aggressive BrCas, using new drugs that individually show great promise in trials in a number of cance
Targeting Complement C5a Receptor 2 As A Disease-modifying Treatment For Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$636,329.00
Summary
Motor neuron disease (MND) is a devasting terminal condition that has no effective treatment. We have identified a novel drug which inhibits an immune protein that can potentially treat MND. In this project we will test this drug in rodent models of MND, and validate its effectiveness in relevant MND immune cells. Ultimately, this project will identify a new potential drug for MND.
Targeted Alternative Splicing: A Common Therapeutic Platform To Treat Inherited Diseases
Funder
National Health and Medical Research Council
Funding Amount
$797,165.00
Summary
Genes consist of exons (protein coding domains) separated by introns (non-coding intervening sequences). It is now evident that not every exon need be included in the gene message to direct synthesis of a functional gene product. This application seeks to identify which exons are essential for gene function and those exons that are "dispensable". Such information will allow personalized therapies to be developed based on splice switching, as we have done for Duchenne muscular dystrophy.
Blood-Brain Barrier Penetrating Antisense Therapy For Spinal Muscular Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$635,005.00
Summary
Spinal muscular atrophy (SMA) is a genetic disease caused by the deficiency of a protein known as survival motor neuron.This results in the degeneration of motor neurons (nerve cells controlling muscles) leading to progressive muscle weakness, paralysis, and eventual death. Currently, there is no known cure for SMA. The aim of proposed research is to develop gene-modifying molecules that prevent degeneration of motor neuron and extend the life-span of mice as a potential therapy for SMA.
Antisense Oligonucleotide Induced Exon Skipping As A Treatment For Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$363,055.00
Summary
Duchenne muscular dystrophy (DMD) is the most common severe muscle wasting disease that affects boys. A defect in the dystrophin gene (typically a frameshift or nonsense mutation) precludes the synthesis of any functional protein. Becker muscular dystrophy (BMD) is a milder condition that also arises from defects in the dystrophin gene but in these cases, the mutations are usually in-frame deletions that allow some functional protein to be synthesised. There have been significant limitations to ....Duchenne muscular dystrophy (DMD) is the most common severe muscle wasting disease that affects boys. A defect in the dystrophin gene (typically a frameshift or nonsense mutation) precludes the synthesis of any functional protein. Becker muscular dystrophy (BMD) is a milder condition that also arises from defects in the dystrophin gene but in these cases, the mutations are usually in-frame deletions that allow some functional protein to be synthesised. There have been significant limitations to dystrophin gene replacement therapies, due to the nature of the target (muscle fibres) and the size and complexity of the gene. This project will investigate an alternative genetic approach in cells expressing dystrophin (this gene is transcribed and processed differently in a variety cell types), whereby antisense oligonucleotides are used to redirect the processing of dystrophin pre-mRNA in the region of the DMD mutation. Although the DMD mutation would still be present at the gene level, the disease-causing mutation would be removed during the processing of the dystrophin pre-mRNA. Once a nonsense mutation has been removed or the reading frame restored from a DMD transcript, the resultant engineered dystrophin mRNA could be translated into a functional Becker-like protein.Read moreRead less