Functional Analysis Of Recently Identified Novel Glaucoma Genes.
Funder
National Health and Medical Research Council
Funding Amount
$519,918.00
Summary
Glaucoma is the commonest cause of irreversible blindness in the world. Recently, through genetic studies in cohorts of blinding glaucoma cases from Australia, our group has found that variants in two genes increase the risk of blinding glaucoma. This project will investigate how these genes contribute to pathological changes in the optic nerve and retina, at the back of the eye, that lead to glaucoma. This knowledge will be useful for developing new strategies to treat glaucoma.
Functional Restoration Of OTC Deficient Primary Human Hepatocytes In A Xenograft Model Using An AAV Vector Uniquely Configured For Impending Clinical Trial Use.
Funder
National Health and Medical Research Council
Funding Amount
$235,525.00
Summary
The aim of this project is to acquire preclinical data which will underpin an international gene therapy trial for severe ornithine transcarbamylase (OTC) deficiency, the most prevalent urea cycle defect in infants and children. In most severe cases, liver transplantation is required for long term survival. We, with colleagues at Stanford University, have recently developed a novel gene therapy tool for optimal targeting of human liver cells which will be tested in a humanised mouse model.
Targeted Knockdown Of Human SOD1 Genes By Non-viral Gene Delivery To Delay Onset And Progression Of ALS
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Amyotrophic lateral sclerosis (ALS) is an illness of nerves resulting in a creeping paralysis and death; there is no effective treatment. We have developed immunogenes consisting of an antibody to target specific nerves and a gene that can affect it. Our immunogene will deliver genes that inhibit a mutant protein causing disease in an ALS mouse model. Successful outcomes of this research will be to encourage development of treatments both before and after the disease has developed.
Genetic And Phenotype Studies Of Partial Epilepsy In Gypsies
Funder
National Health and Medical Research Council
Funding Amount
$646,136.00
Summary
Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies ....Epilepsy is one of the most common serious neurological disorders, which affects more than 50 million people worldwide. Genetic research, with a major contribution from Australian researchers, has led to the discovery of many rare forms of the disease caused by mutations in single genes of large effect. However, the vast majority of cases worldwide belong to the so-called genetically complex forms, involving multiple interacting genes and environmental factors. The genetically complex epilepsies have proved particularly difficult to understand and the numerous genetic studies conducted so far have failed to produce important and replicable results. It is becoming increasingly clear that enormous genetic heterogeneity, with many rare mutations occurring in different affected subjects, will be a major obstacle to understanding the molecular basis of complex epilepsies. In this context, genetically isolated populations, which stem from a small number of ancestors, can be particularly helpful and revealing, since their limited genetic diversity means that the number of genes involved in causing complex epilepsies may be smaller and shared between individuals and families. In this study, we will analyze affected families, as well as non-familial cases of epilepsy, from a genetically isolated population - the European Roma-Gypsies. We will determine the number of potential susceptibility genes involved in familial forms, the overlap and differences between families, as well as the contribution of the genes identified in families to the development of sporadic epilepsy.Read moreRead less
Minimally-invasive Gene Delivery Of A Novel Inhibitor Of Retinal Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$883,883.00
Summary
Excessive growth of blood vessels in the eye causes vision loss and can only be treated with lasers or painful and frequent injections into the eye. Vasostatin is a specific inhibitor of angiogenesis and a promising agent for the management of ocular neovascularisation. We will provide pre-clinical evidence that gene delivery of vasostatin-like peptides is an effective therapeutic strategy and it has potential to revolutionize the current ophthalmic care of age-related macular degeneration.
Defining The Changes In Cell Biology Caused By PRESENILIN Truncations Associated With Different Diseases
Funder
National Health and Medical Research Council
Funding Amount
$622,886.00
Summary
Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be requir ....Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be required for the development of treatments.Read moreRead less
Gene Discovery And Pathobiology In Muscle Diseases
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
I aim to find the genetic causes of muscle diseases that are lethal or severely debilitating. These diseases result in a significant burden to the affected individuals and their families and also on Australia’s Health care system. A genetic diagnosis provides families with answers, allows family planning, such that couples do not have another affected child, enables appropriate clinical management and gives researchers evidence as to how to develop treatments.
Improving The Genetic Diagnosis Of Neuromuscular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$338,836.00
Summary
Neuromuscular disorders involve progressive muscle weakness where currently there are no effective specific treatments, and only a diagnostic rate of ~60%; thus emphasising the great need for research into gene discovery and disease mechanisms. The use of genomics technologies can increase the diagnosis rate but challenges still remain. This project aims to address these challenges by developing tools and workflows to improve the diagnostic rate of neuromuscular diseases.
Applying Gene Therapy Towards Limb Girdle Muscular Dystrophy 2I And Other Human Muscle Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$347,264.00
Summary
Therapeutic replacement of small, normal sections of the dystrophin gene can prevent muscle wasting in young dystrophic mice with mutations in dystrophin. This project attempts to apply the same principle to treat another inherited muscle disorder, caused by mutations in the FKRP gene. This approach can also potentially be used to enhance muscle regeneration and treat age related muscle atrophy, or synergistically applied with other therapies that target specific genetic mutations.