Investigating Mechanisms Of Axonal Pathology Following Oligodendrocyte Apoptosis: Avenues For Neuroprotection In Early MS
Funder
National Health and Medical Research Council
Funding Amount
$678,138.00
Summary
Recent research suggests that Multiple Sclerosis could first be triggered by the death of a type of brain cell called an oligodendrocyte. These cells insulate nerve cells in the brain which help them function normally. We will test the idea that death of oligodendrocytes impairs nerve cell function by causing inflammation and by depriving nerve cells of energy. We will determine whether preventing inflammation and feeding the nerve cells an alternative source of energy can restore normal functio ....Recent research suggests that Multiple Sclerosis could first be triggered by the death of a type of brain cell called an oligodendrocyte. These cells insulate nerve cells in the brain which help them function normally. We will test the idea that death of oligodendrocytes impairs nerve cell function by causing inflammation and by depriving nerve cells of energy. We will determine whether preventing inflammation and feeding the nerve cells an alternative source of energy can restore normal function.Read moreRead less
Unravelling The Mechanism Coupling Synaptic Activity With Neurotrophin Signaling In The Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$640,815.00
Summary
Although active brain cells are known to survive for much longer than inactive ones, the mechanism underpinning this essential process has remained elusive. We have uncovered a direct coupling between neuronal activity and survival signals. The purpose of this grant application is to establish the molecular mechanism underpinning this coupling and understand how neuropathic pathogens manage to harness it with devastating effects to the brain.
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
Connectivity Of Regenerating Axons Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Our objective is to thoroughly investigate the connections made by regenerating nerve fibres in mice which are treated with specific compounds to inhibit scarring as well as with active exercise following spinal cord injury. This will provide evidence of the potential of these compounds as a therapeutic intervention. Understanding how the nervous system rewires following exercise intervention will provide insights as to how new connections can be shaped to ensure optimal recovery of function.
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.
The Combined Use Of Transplantation And Gene Therapy Techniques To Promote Regeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$521,026.00
Summary
Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce gen ....Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce genes into cells, a method that allows targeted supply of molecules to the injured brain. Gene and cell therapy may eventually be of clinical benefit to injured patients. In a range of different experiments we will combine two different gene therapy approaches, various pharmacological agents and novel transplantation strategies in attempts to enhance the survival of affected nerve cells and promote the regrowth of damaged nerve fibres across injury sites in the injured adult rat visual system. Long-term vector-mediated expression of growth factors in neurons and in grafts may 'trap' regenerating axons, potentially reducing their outgrowth into distal, denervated target areas. It is therefore important to determine if temporal regulation of growth-promoting genes has additional beneficial effects on the ability of regenerating neurons to recognise and selectively regrow axons into appropriate CNS targets. An additional series of studies will thus be undertaken. We will test a new generation of regulatory vectors in which it is possible to switch the virally encoded genes on or off and thus control the level and timing of gene expression over a therapeutic range. We will then determine if the use of these regulatory viral vectors results in more consistent and robust growth of nerve fibres with better reconnections, in the longer term leading to better recovery of function.Read moreRead less
Signalling Mechanisms Regulating Neurogenesis And Neurite Outgrowth
Funder
National Health and Medical Research Council
Funding Amount
$486,000.00
Summary
Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emer ....Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emerged in recent years, that has led to the view that repair of the central nervous system following injury of disease may indeed be a possibility. Effective neural repair is likely to require a multi-factorial approach, including blockage of neuronal death, replacement of lost neurons by neural stem cells, and regulation of appropriate subsequent neurite outgrowth and formation of correct connections. We have shown that a regulator of cytokine signaling, SOCS2, promotes neuronal differentiation and neurite outgrowth. This project aims to continue our investigations of the role of SOCS2 and interacting factors in regulating neuronal differentiation as well as substantially expanding our investigations into the role of SOCS2 in regulating neurite outgrowth, using both in vitro and in vivo models. An understanding of the mechanisms involved in these processes may allow us to derive therapies for the repair of the nervous system after injury or disease.Read moreRead less