Developing Exon Replacement Gene Therapy To Cure Rett Syndrome: An Innovative Model For Neurodevelopmental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$475,105.00
Summary
There is no cure for neurodevelopmental disorders such as Rett syndrome which is caused by mutations in the MECP2 gene. Gene therapy is ineffective due to the 'Goldilocks' effect where too little, as well as too much expression of MECP2 causes disease. Here a gene editing therapy will be tested in patient cells and mouse model that will maintain the normal cellular expression of MECP2 by cutting out the mutated regions of the gene (exons) and replacing them with repaired copies.
Functional Brain Age Measurement In Children And Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$700,433.00
Summary
An important aspect of medicine is measuring the function of the human body. It is often advantageous to convert complex functional measures into simpler, intuitive measures such as 'age'. We can compare functional age to chronological age to diagnose disease. In this project, we will build an estimate of 'brain age' in children and adolescents using recordings of the electrical activity of the brain. We will test this 'brain age' as a diagnostic tool in several neurological disorders.
Genetic testing of IVF embryos promises to improve success but shows no effect of live-birth rates. Many embryos are mosaic: containing cells with correct and incorrect chromosome numbers. Current testing is an invasive biopsy which fails to diagnose how many cells are abnormal in the cells that develop into the baby. Here we will use imaging to determine the ratio of abnormal:normal cells resulting in a non-invasive diagnostic that will improve IVF success.
A Cellular Identity Crisis: Deciphering How Mammary Epithelial Cells Form And Maintain Their Identity
Funder
National Health and Medical Research Council
Funding Amount
$843,826.00
Summary
The ability to regenerate human organs from adult cells efficiently and without error is a major goal of biomedical research in Australia, with significant economic benefits. As one of the most regenerative organs in a woman's body, the breast is an excellent model to study mechanisms that underpin tissue growth and regrowth. Moreover, as these pathways are often hijacked by cancer, this research has important implications for the development of new targeted therapies to treat breast cancer.
Intergenerational Impacts Of Paternal Immune Activation On Brain Function And Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$997,690.00
Summary
We recently discovered that infection of male mice with a parasite (Toxoplasma gondii) before conception can change the epigenetic information in the sperm and alter behaviour of the offspring. This is the first evidence that pathogenic infection in males can affect the next generation. We will investigate how infection with other major pathogens, including bacteria and the virus causing COVID-19, may affect sperm epigenetics and offspring health, including their brain function and dysfunction.
Narcolepsy With Cataplexy: A Brain Orexin Replacement Strategy
Funder
National Health and Medical Research Council
Funding Amount
$810,784.00
Summary
Narcolepsy with cataplexy is a debilitating, life-long sleep-wake disorder, caused by the irreversible loss of the brain peptide 'orexin'. There is no satisfactory and safe treatment. We aim to develop an orexin analogue, delivered directly to the brain of sheep (relevant in size and translatable to patients) by a programmable pump to timely activate the orexin 'wake-up' switch. This innovative precision medicine project will significantly improve the quality of life of narcolepsy patients.
Creating A Phenotypic Catalogue Of Synaptic Vesicle Cycling Disorders
Funder
National Health and Medical Research Council
Funding Amount
$876,975.00
Summary
Developmental disorders affect 2-5% of children. In order to understand how these mutations will likely affect neurological function in these individuals, and to develop a tailored care and treatment program, we must first understand how these mutations affect neuronal communication. This research program will identify the underlying cause of neurological dysfunction in a subset of these disorders (synaptic vesicle cycle disorders), affecting 1200-3000 children in Australia alone.
The Future In Our Hands: Screening For Preclinical Alzheimer's Disease By Analysing Hand Movements
Funder
National Health and Medical Research Council
Funding Amount
$899,782.00
Summary
Alzheimer's disease (AD) starts damaging the brain 10-20 years before memory problems begin. By the time of diagnosis, it is hard to treat because the damage is so severe. We need a way to detect AD much earlier. We will develop a simple new computer test to detect early signs of AD by recording and analysing hand movements. Then people can start prevention earlier and scientists can research better treatments to improve people's quality of life and reduce the number of people with dementia.
Ataxia-Telangiectasia: An Emerging Role For Inflammation In Driving Neurodegeneration And Premature Ageing
Funder
National Health and Medical Research Council
Funding Amount
$437,436.00
Summary
Ataxia-Telangiectasia (A-T) is a devastating genetic disease that arises in early childhood and causes patients to die in their twenties. To date there is no cure, and therapeutics are desperately needed. This project will use state-of-the-art brain organoids derived from stem cells of A-T patients in order to better understand this disease and evaluate novel drugs that target the molecular mechanisms that drive chronic inflammation and brain neurodegeneration in children with A-T.
Finely Tuned Glutamate Receptor Inhibitors As Novel Therapeutics For Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$1,168,829.00
Summary
Neurodegenerative disorders are among the leading causes of death and disease burden. New drugs are needed to treat both symptoms and disease progression. This project aims to understand the properties of different drug-like compounds to inhibit proteins on the surface of brain cells (glutamate receptors) to impact disease progression and symptoms in a preclinical disease models. The project will yield a better understanding of how best to target glutamate receptors for therapeutic effect.