Mechanism Of Action Of A Quinazolinone In Models Of PD
Funder
National Health and Medical Research Council
Funding Amount
$667,548.00
Summary
By the time symptoms of Parkinson's disease (PD) appear, 60-70% of the cells in a crucial part of the brain called the substantia nigra have been destroyed and within a few years of diagnosis, most of the remaining cells have died. This project investigates the causes of this cell loss and a how a new class of compounds could interrupts the process. Success in achieving the aims of this proposal will add to our knowledge of the causes of neuronal death in PD
Molecular Mechanisms Of Testosterone Action On Midbrain Dopamine Neuron Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$339,739.00
Summary
Schizophrenia is characterized by psychosis, social and occupational dysfunction and cognitive deficits. Males are more often diagnosed and more severely impaired than females. Onset in males is most frequent during adolescence, a time of increasing sex hormones. We ask, how do sex hormones act on the adolescent male brain to impact the onset and symptoms of schizophrenia? The answer will allow development of gender and age-specific interventions to prevent onset or ameliorate symptoms.
The Final Common Channel: Measurement Of Nerve Excitability In Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$301,376.00
Summary
Epilepsy may be due to either one single genetic mutation or a combination of several gene-environment interactions, affecting how ion channels function. It is not possible to directly interrogate channels in the living human brain but, because similar channels are found in peripheral nerve, much may be learned about aberrant channel function from peripheral nerve. This project aims to measure peripheral nerve excitability in epilepsy patients, using it as a marker of the final common pathway of ....Epilepsy may be due to either one single genetic mutation or a combination of several gene-environment interactions, affecting how ion channels function. It is not possible to directly interrogate channels in the living human brain but, because similar channels are found in peripheral nerve, much may be learned about aberrant channel function from peripheral nerve. This project aims to measure peripheral nerve excitability in epilepsy patients, using it as a marker of the final common pathway of channel dysfunction.Read moreRead less
Structure-based Drug Design For Neuroprotection From Traditional Chinese Medicine
Funder
National Health and Medical Research Council
Funding Amount
$245,968.00
Summary
In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative di ....In the proposed research, three novo approaches for drug discovery will be explored: 1) The important neurodegenerative disease relevant protein JNK3 crystals will be used as the probe to fish out the potential inhibitors from Traditional Chinese Medicine (TCM); 2) Instead of individual drug components, the mixture of TCM will be used directly; 3) The composition of a TCM library are not randomly chosen but have been used in China for hundreds to thousands of years in curing neurodegenerative disease.Read moreRead less
Development Of Pthaladyn-based Dynamin I-selective Inhibitors For Treatment Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$564,310.00
Summary
About 1% of the World�s population suffers from epilepsy; 30% fail to respond to anti-epileptic drugs (AED). Current AED development pathways have changed little in the past 20 years with the majority of current AEDs dampening the release of crucial chemical signals 24/7. Our new drugs, which inhibit a protein called dynamin, are only recruited at the onset of a seizure. Our approach will significantly enhance the day to day lives of those afflicted by epilepsy.
Inhibitory Neurotransmitter Receptors As Therapeutic Targets For Chronic Pain And Anxiety Disorders
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
There are currently few effective long-term treatments for chronic pain and anxiety disorders. Here we propose to develop innovative therapies for both of these debilitating neurological disorders. In addition, we plan to improve our current understanding of how these disorders occur in the first place. This may identify novel potential therapeutic strategies for treating pain, anxiety and a host of other neurological disorders.
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.
Ecstasy, Methamphetamine And Their Combination: Assessment Of Adverse Effects
Funder
National Health and Medical Research Council
Funding Amount
$384,250.00
Summary
MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour a ....MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour and memory impairment. However the link between MDMA and METH use and subsequent brain damage is still very controversial. Recently, we have found that when MDMA and METH are combined, a particularly toxic effect is seen with very high body temperatures and lasting adverse effects on mood and brain function. This is a major cause for concern because of evidence that many Australian drug users are combining METH and MDMA on a regular basis. This project will investigate the short and long-term effects of MDMA, METH and METH-MDMA combinations. Phase 1 is aimed at investigating whether different doses of the drugs lead to lasting changes in mood, behaviour and brain function and to compare the relative toxicity of the three treatments. Phase 2 will determine whether lack of fluid intake, high environmental temperatures and advanced age are risk factors in determining the toxicity of MDMA and METH. Phase 3 will assess whether the toxicity of these drug treatments depends upon whether an animal takes the drugs voluntarily or whether they are injected with the drug by the experimenter. The final part of the project will use a wide variety of advanced techniques to track the brain damage caused by these drug treatments given under a range of conditions. The significance of this project will be in increasing our understanding of how MDMA and METH affect the brain and behaviour and how the harms posed by these drugs may be predicted and therefore minimised.Read moreRead less
Genomics Of Antiepileptic Drug-induced Stevens Johnson Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$500,817.00
Summary
Epilepsy affects 3% of people. Severe skin reactions to anti-epileptic drugs are unpredictable and potentially fatal. This project aims to better understand the complex genetic architecture of these reactions using the latest sequencing platforms applied to a unique collection of samples, followed by functional analysis. The findings will enhance the practice of precision medicine in epilepsy treatment, shed light on the mechanisms of these reactions, and inform better drug design in the future.
Slowing Progression Of Alzheimer’s Disease By Modulating The Kynurenine Pathway
Funder
National Health and Medical Research Council
Funding Amount
$578,460.00
Summary
Chronic inflammation in the brain in known to be a factor in the progression of Alzheimer's disease. We are exploring if blocking a particular enzyme in a biochemical pathway involved in inflammation, can improve symptoms, or slow progression, of the disease in animal models of AD. If results are as expected, our proposal has the potential to generate a new a therapy for AD.