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
Astrocytic Contributions To Tissue Damage And Dysfunction In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$275,810.00
Summary
Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to o ....Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to open up new avenues for ameliorating damage and improving outcomes for stroke patients. Astrocytes are one of the major populations of cells in the brain. They play key roles in supporting normal brain function and protecting nerve cells in the brain. Because of their many functions, these cells offer considerable potential as a therapeutic target in stroke. Unfortunately, the responses of astrocytes in this disorder are poorly understood due partly to a lack of techniques to distinguish their contributions from that of other cells in the brain. We have recently designed a novel system using antibodies to deliver genes into selected populations of nerve cells in the nervous system and thus to selectively alter the function of these cells. In the proposed study, we will adapt this technique to selectively modify gene expression in astrocytes. We will then apply the procedure to determine the consequences of altering key functions in astrocytes on the brain damage and behavioural changes that develop in an animal model of stroke. The successful completion of this research will provide a powerful means to investigate the function of astrocytes, not only in diseases such as stroke but also in normal brain. We will also gain novel insights into the astrocytic role in the damage and dysfunction resulting from stroke that have potential applications in developing new therapies.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.
Salt (sodium) is an essential electrolyte. Our convincing and complementary findings provide compelling evidence for a link between evolutionarily ancient “instincts” and substance abuse. This proposal is translational, including studies in opiate dependent humans. Our studies will establish how and where in the brain endogenous opioids are implicated in the gratification of salt appetite, how salt appetite is altered in opiate dependency and if salt appetite recovers following opiate withdrawal
Lipophilic Iron Chelators As Potential Therapeutic Agents In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$616,537.00
Summary
The impaired coordination and tremors experienced by the 64,000 Australians with Parkinson’s disease make managing life at work and home difficult. With 240,000 Australians projected to be living with Parkinson’s disease by 2033, the discovery of agents that slow or stop disease progression is urgent. Iron in the brain has been implicated in Parkinson’s disease. In this project, the performance of new low toxicity agents in altering brain iron distribution will be studied as potential drugs for ....The impaired coordination and tremors experienced by the 64,000 Australians with Parkinson’s disease make managing life at work and home difficult. With 240,000 Australians projected to be living with Parkinson’s disease by 2033, the discovery of agents that slow or stop disease progression is urgent. Iron in the brain has been implicated in Parkinson’s disease. In this project, the performance of new low toxicity agents in altering brain iron distribution will be studied as potential drugs for Parkinson’s disease.Read moreRead less