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Advanced Polymer Systems For The Delivery Of Anti-Epileptic Drugs To The CNS
Funder
National Health and Medical Research Council
Funding Amount
$593,375.00
Summary
The use of organic conducting polymers as novel platforms for drug delivery is expected to provide significant improvements in our ability to treat and manage illnesses and trauma. A number of novel drug-loaded platforms with the introduction of a conducting polymer component to enable electrically stimulated release, generated physiologically (by onset of an epileptic seizure) or by a bio-corrosion process (stents) provides innovative drug release systems powered autonomously.
Development Of Small Molecule Isoform-Selective Dynamin Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$85,526.00
Summary
Dynamin has roles in nerve cell communication and in cell division. There are 3 dynamin genes: dynamin I in brain; dynamin II in all cells; and dynamin III in brain and testes. Determination of potential selectivity of small molecule dynamin inhibitors for each dynamin gene can provide a basis for the development of new antiepileptic drugs which are specific for dynamin I and thus neuronal tissues, as well as new anticancer drugs that target dynamin II in nonneuronal cells.
Whole Genome Pharmacogenomics Study Of Susceptibility Of Birth Defects In Children Born To Mothers Taking Anti-Epileptic Drugs
Funder
National Health and Medical Research Council
Funding Amount
$663,160.00
Summary
This project will investigate for genes that determine why certain women have an increased risk of having a baby with a birth defect if they become pregnant while being treated with a medication for epilepsy. Subjects will be recruited from the Australian Pregnancy Register, the findings validated using subjects from the UK Epilepsy and Pregnancy Register. The study will comprehensively examine for both common and rare changes in genes across the entire human genome.
I am a lab-based neurochemist-cell biologist with expertise in protein chemistry and pharmacology. My research focuses on the dynamin family of proteins in the endocytosis of synaptic vesicles and in the molecular mechanisms of synaptic transmission in th
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.
Carbon Dioxide As A Treatment For Seizures In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$878,389.00
Summary
This study aims to introduce a simple and effective treatment to prevent brain damage from seizures in babies using CO2. Neonatal seizures remain a major clinical problem worldwide and are associated with poor brain outcomes and significant risk of death. Recent trials in human adult epileptics show rapid and effective seizure suppression following the use of CO2. This therapy will significantly impact long-term outcomes for affected babies and reduce the burden of care for families and society.
How Does Chronic Epilepsy Result In Cardiac Electrophysiological Dysfunction?
Funder
National Health and Medical Research Council
Funding Amount
$737,112.00
Summary
Cardiac dysfunction is common in epilepsy, and could be an important contributor to the increased risk of sudden death in people with epilepsy (SUDEP). In this grant we will investigate: when changes in the cardiac function develop in relation to the epilepsy; if people with chronic epilepsy have similar changes; and what effect seizures and epilepsy has on the nerves innervating the heart. The outcomes have the potential to motivate new treatments and prevention for this important problem.
Mechanisms Of Synaptic Vesicle Endocytosis Revealed By Its Regulatory Phosphoproteome
Funder
National Health and Medical Research Council
Funding Amount
$545,216.00
Summary
The nerve cells in our brains are in constant communication to sustain life. Communication involves electrical stimulation of one nerve cell which then responds by releasing chemical messengers, from vesicles, onto the next cell. Our research focuses on the mechanism of recycling of vesicles. Targeting this mechanism is a way to gain fundamental knowledge of how to intervene medically when communication fails, or when communication needs to be dampened, such as in some neurological diseases.
Dynamin Inhibitors As Tools For Dissecting The Endocytic Pathway In Neurons
Funder
National Health and Medical Research Council
Funding Amount
$470,250.00
Summary
Nerve cells communicate by the release of neurotransmitters which are packaged in synaptic vesicles inside nerve endings. There is a finite number of vesicles, so they are recycled (endocytosis) for reuse. Some human neural diseases hijack the endocytic pathway for entry of pathological peptides, proteins or viruses to paralyse, kill or infect neurons. Our overall aim is to control nerve communication to ultimately allow us to treat disorders of nerve communication like epilepsy. At its most ext ....Nerve cells communicate by the release of neurotransmitters which are packaged in synaptic vesicles inside nerve endings. There is a finite number of vesicles, so they are recycled (endocytosis) for reuse. Some human neural diseases hijack the endocytic pathway for entry of pathological peptides, proteins or viruses to paralyse, kill or infect neurons. Our overall aim is to control nerve communication to ultimately allow us to treat disorders of nerve communication like epilepsy. At its most extreme, completely blocking endocytosis quickly results in a complete block in nerve communication. Therefore slowing it down (rather than blocking) might be a means to control some neural diseases. For example, a seizure is the uncontrolled firing of neurons. The main mechanisms controlling endocytosis converge on the protein dynamin. Dynamin can assemble into a tiny, tightly wound helix or spring. When energy (GTP hydrolysis) is applied to the nanospring it rapidly releases to cleave off empty recycling synaptic vesicles from the cell wall back into the neuron. Our premise is that blocking the nanospring may lead to a new generation of antiepileptic drugs. To achieve this we have already discovered the first chemical inhibitors of dynamin. In this project we will determine how they work, by showing that they target distinct sites in dynamin. We have embarked on an ambitious chemical synthesis program to greatly improve the potency and specificity of the inhibitors. We will expand this with an iterative approach using combinatorial chemistry. When applied to neurons, the drugs appear to be the first endocytosis inhibitors. Will test our proposal that they will reveal multiple points of action of dynamin in various stages of endocytosis. This project will prove the principle that the development of anti-dynamin drugs could lead to the first anti-endocytic drugs. This has the potential to lead to future development of targeted antiepileptic and anticancer drugs.Read moreRead less
Molecular Mechanisms Of Tumour-associated Seizures
Funder
National Health and Medical Research Council
Funding Amount
$426,498.00
Summary
Seizures commonly develop in patients with brain tumours. Despite tumour resection, patients continue to experience seizures. Furthermore, patients can often be resistant to treatment with anti-epilepsy medications adding further burden to patient suffering, decreasing quality of life and overall survival. The cause is unknown and we propose identifiable causes are involved. This will provide effective targets for the development of medications for the treatment of these seizures.