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.
Role Of Dynamin In Modes Of Synaptic Vesicle Endocytosis
Funder
National Health and Medical Research Council
Funding Amount
$905,985.00
Summary
Neurons communicate by neurotransmitter release from synaptic vesicles stored in nerve endings. There is a finite vesicle number, so they are recycled (endocytosis) by dynamin. Our aim is to reveal the molecular mechanisms underlying endocytosis to better understand diseases of the synapse like epilepsy. We propose that two forms of the dynamin gene mediate two forms of endocytosis, one of which is activated only under conditions of high neuronal firing, such as occurs during a seizure.
Functional Neurogenesis In The Injured Neocortex Of The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$966,048.00
Summary
Research over the past couple of decades has revolutionised our understanding of the capacity of the brain to generate new cells, especially following an injury. However, what does remain controversial is whether this phenomenon occurs in all areas of the brain, especially following a severe traumatic brain injury or stroke. This project will examine whether the outer surface of the brain has the potential to generate new cells following a brain injury and whether they become functional.
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
We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being pas ....We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being passively deflected by objects. Deflection results in inputs to the brain that are processed to form the neural basis for very finely detailed perceptual behaviour. In rats, with impoverished visual and auditory senses, the whiskers are the major sensory system for interacting with the world, and are used in navigating the environment and in finding and distinguishing foods. Thus they contribute strongly to the remarkable success of this species. This elegant sensory system has a number of advantages that make it a very good model for the study of brain mechanisms responsible for active fine-grain sensory function. We plan to take advantage of the unique features of this system to define the information processing that occurs in the cortex in this elegantly complex system. This will address an issue relevant to all sensory systems - namely the neural basis of complex fine grain perceptual behaviour. Understanding the mechanisms underlying active tactile perception also has relevance to clinical conditions involving deficits in active touch e.g., in diabetic polyneuropathy (which eventually affects ~50% of diabetics), in leprosy (in which an early sign is damage to active touch). Knowledge of the core brain processes in active touch gained in this study could eventually underpin the ameliorative technologies for such deficits.Read moreRead less
Roles Of Peripherally Derived BDNF In Regeneration Of Spinal Cord And The Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by increasing the production of neurotrophic factors within nerves. Successful complet ....Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by increasing the production of neurotrophic factors within nerves. Successful completion of this project will help understanding the mechanism of how neurotrophic factors work on regeneration and developing the effective way to improve regeneration of the injured spinal cord.Read moreRead less
The Contribution Of IL-1 Signalling To Long-term Neurodegeneration, Epilepsy And Neurocognitive Outcomes Following Traumatic Injury To The Paediatric Brain
Funder
National Health and Medical Research Council
Funding Amount
$394,670.00
Summary
Epilepsy is a common, debilitating consequence of brain injury in children, however little is known about factors which trigger its development. This proposal investigates the contribution of the acute inflammatory response to long-term neuronal loss, functional outcomes and seizure activity after paediatric brain injury. Understanding how epilepsy and brain damage progresses after injury will aid the development of drugs to improve long-term outcomes in brain-injured children.
Viral-mediated Modulation Of BDNF Expression In Motor Neurons To Promote The Recovery Of Hand/digits Function In A Rat Model Of Spinal Cord Injury That Impairs Normal Grasping Action.
Funder
National Health and Medical Research Council
Funding Amount
$341,427.00
Summary
This project seeks to lure injured axons towards motor neurons, a process that is essential for the recovery of motor function. BDNF gradients will be created along the injured axons path. Axons will have to elongate to reach the first source of BDNF. They will need to elongate even more to get to the next source of BDNF, hence bringing them each time closer to their lost targets. This gene therapy scenario has the potential to bring gene therapy a step closer for human spinal cord injury.