The Clinical Features, Causes And Diagnosis Of Severe Epilepsies Of Infancy: A Population-based Study
Funder
National Health and Medical Research Council
Funding Amount
$227,261.00
Summary
Severe epilepsies of infancy (SEI) are characterised by frequent seizures and are often resistant to treatment. The prognosis is typically poor. The cause is unknown in many infants. This study will identify genes and brain malformations causing SEI, determine the frequency and clinical features of each cause, and measure the diagnostic yield of genetic testing and brain imaging. The findings will improve timely diagnosis of SEI and guide research priorities for development of novel therapies.
Clinical Utility And Cost-effectiveness Of Genome Sequencing For Refractory Epilepsy In Children And Adults: A Multicentre Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$720,609.00
Summary
A large number of genomic variants have been found to underpin common types of epilepsy and to predict adverse drug reactions. However, the adoption of genomic testing in the routine management of epilepsy is hampered by uncertainties around its clinical utility and cost-effectiveness. This randomised controlled trial aims to determine the diagnostic efficiency, clinical and psychosocial impact, and cost-effectiveness of whole genome sequencing for refractory epilepsy in children and adults.
Precision Medicine For Epilepsy And Beyond: From Discovery To Implementation And Evaluation
Funder
National Health and Medical Research Council
Funding Amount
$487,891.00
Summary
The theme of this Fellowship is to improve treatment outcomes using a genomic-based Precision Medicine approach. This goal will be achieved by 3 closely linked projects that harness the power of gene sequencing and advances in biosensor technology, coupled with careful clinical and health economic evaluation. While the emphasis is on epilepsy, the research will extend to other major disease areas of global health significance. The potential socioeconomic impact of these innovations is enormous.
An Integrated “omic” Approach To Neurodevelopmental Disorders Using Disease-discordant Monozygotic Twins
Funder
National Health and Medical Research Council
Funding Amount
$84,800.00
Summary
This project targets neurodevelopment disorders such as autism spectrum disorder, cerebral palsy and epilepsy and focuses on studying the environmental factors (epigenetics) affecting the disease mechanisms in these disorders. The study will be performed on twin samples and will help in the diagnosis of the disease risk at an earlier stage. It will also help to understand the causes of these important neurological diseases.
SELECTIVE VULNERABILITY IN ALZHEIMER’S DISEASE AND RELATED DISORDERS: MECHANISM OF TAU PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$1,072,324.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to 730,000 by 2050. The direct costs for health and residential care alone exceed $6.6 billion per annum. By identifying genes that protect degenerating neurons in the Alzheimer brain, a deeper understanding of the underlying processes will be gained and therapeutic targets will be defined that will assist in developing a therapy for a yet uncurable disease.
Functional Genomics Approach To Extend Lifespan While Preventing Age-related Cognitive Decline
Funder
National Health and Medical Research Council
Funding Amount
$772,600.00
Summary
In our ageing population, preventing age-related neurological decline is one of the central medical challenges of the 21st century. Here we use human population data obtained from people who reached 90 years of age free of any disease, or patients who suffer from dementia, combined with functional genomics studies in animals to pinpoint new genes that can be targeted to extend lifespan while preserving neurological function in these extended years of life.
Alzheimer's Disease And Related Disorders: Mechanism Of Tau Pathology In Established And Novel Transgenic Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$423,017.00
Summary
Alzheimer's disease (AD) is a devastating neurodegenerative disease for which no cure is available. It affects more than 15 million people worldwide. There are estimates that by 2040, approximately 500'000 Australians will suffer from AD, with associated health costs of about 3% of the GDP. AD is characterized by two major brain lesions, beta-amyloid plaques and neurofibrillary tangles (NFTs). The latter contain a protein called tau which is in a fibrillar and highly phosphorylated state. We wer ....Alzheimer's disease (AD) is a devastating neurodegenerative disease for which no cure is available. It affects more than 15 million people worldwide. There are estimates that by 2040, approximately 500'000 Australians will suffer from AD, with associated health costs of about 3% of the GDP. AD is characterized by two major brain lesions, beta-amyloid plaques and neurofibrillary tangles (NFTs). The latter contain a protein called tau which is in a fibrillar and highly phosphorylated state. We were the first to establish a transgenic animal model of pre-tangles and, together with Dr. Hutton's laboratory, of NFT formation. We could further show that injections of beta-amyloid into brains of our tau mutant mice enhanced the NFT pathology in these mice. By Functional Genomics we identied genes and proteins, which are induced by tau expression. The specific aim of this proposal is to determine whether oxidative stress enhances the tau pathology in our tau mutant mice and whether distinct brain areas are particularly susceptible to this kind of stress. The reason for addressing this question is twofold: On the one hand, we have found in our mice that reactive oxygen species are increased, secondly it is known that some brain areas in the AD brain are degenerating, whereas others are not. A second aim is to develop novel tau transgenic models where individual interactions of tau with cellular proteins are disturbed. Finally, we want to determine whether the two kinases BMX and FAK and the phosphatase PPV regulate tau phosphorylation in vivo. Together, we hope that our efforts lead to a better understanding of the pathogenic mechanisms in AD and related disorders. As pathocascades are likely to be shared between a range of diseases, these findings may also contribute to other fields of research, such as Parkinson's disease. Ultimately, these efforts will assist in the development of a safe treatment of AD.Read moreRead less