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.
A Breakdown Of Cortical Homeostasis In Depression: A Focus On The Anterior Cingulate
Funder
National Health and Medical Research Council
Funding Amount
$625,629.00
Summary
Major depressive disorders affect 20% of the Australian population. Some symptoms of major depressive disorders arise because of a dysfunction of the human brain, particularly the cortex. Our studies show there are biochemical changes in the anterior cingulate cortex in people with mood disorders. We will now extend our studies to show there is a breakdown in the balance between neurotransmitter and neuroinflammation pathways in the anterior cingulate cortex in major depressive disorders.
Complement Activation As A Therapeutic Target And Clinical Biomarker For Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$497,941.00
Summary
Parkinson’s disease is the second most common neurological disease in Australia, yet there is no treatment to slow disease progression. Our study is investigating inflammation within the brain as a major contributing factor in Parkinson’s disease. We will examine this inflammatory pathway in human patients suffering from Parkinson’s, and will test a novel anti-inflammatory drug in animal models of Parkinson’s disease, in order to identify a novel treatment to reduce disease pathology.
Novel Radiolabelled Peripheral Benzodiazepine Receptor (PBR) Ligands For Imaging And Treating Neuroinflammation
Funder
National Health and Medical Research Council
Funding Amount
$425,460.00
Summary
Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destructio ....Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destruction. The ability to pickup early signs of injury or to measure destructive changes to glial cells in the brain using noninvasive imaging techniques would be of great value in the clinical diagnosis and management of neurodegenerative disease. The ubiquitous nature of these activated microglia also makes the microglia a target for the development of pharmacological approaches to the treatment or prevention of many central nervous system diseases. Researchers at ANSTO and the ANU have developed a novel class of molecules, which target a specific protein called the peripheral benzodiazepine receptor or PBR which is enhanced in damaged glia. Radiolabelled analogues of these molecules have demonstrated a strong correlation between inflammation and the expression of this receptor in various animal models of inflammation and neurodegeneration. Furthermore, these molecules have the potential to inhibit further damage to these glial cells and could potentially slow down the progression of the disease. Therefore, further development of these molecules both as radiopharmaceuticals for noninvasive medical imaging and-or as inhibitors of microglial activation could have a significant impact on the understanding, management and treatment of neurodegenerative disease.Read moreRead less
Does IRAP Contribute To Alzheimer's Disease Pathology?
Funder
National Health and Medical Research Council
Funding Amount
$743,042.00
Summary
Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or pro ....Alzheimer’s disease is a progressive brain disease which is results in memory loss and cell death. All currently prescribed drugs treat the memory loss but are unable to stop the deterioration of brain cells. We have developed a class of drugs that reverse memory loss. These drugs target a protein called insulin-regulated aminopeptidase, IRAP. We recently found that these drugs also reduce the disease pathology. This research proposal aims to investigate the role of IRAP in the initiation or progression of Alzheimer’s disease pathology.Read moreRead less
Preclinical Development Of Complement C5aR Antagonists For The Treatment Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$593,326.00
Summary
There is no cure for Motor Neuron Disease (MND) resulting in 2 Australian’s dying each day. Modification of the inflammation is one potential means of slowing MND. Our research team has identified a new series of potent anti-inflammatory compounds that may have potential to treat this disease. Our project will test these compounds in animal models of MND, and validate their usefulness in human MND samples. Ultimately, this work may contribute to the discovery of a new treatment for MND.
Controlling Neuroinflammation In Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$639,577.00
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, with 269,000 Australians currently diagnosed with AD and is expected to soar to about 981,000 by 2050. AD accounts for greater than 60% of all cases of dementia. This grant investigates the role that neuroinflammation plays in the progression and exacerbation of AD and will identify new therapeutic strategies to combat this insidious disease.
Understanding Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,043,216.00
Summary
This project opens a new line of enquiry into the cellular signalling mechanisms involved in the progression of AD and establishes whether targeting the involvement of type-1 IFN signalling influences the evolution of AD. New and novel approaches are clearly required to treat AD. Importantly, we believe that neuroinflammation is common to all causes of dementia and targeting the neuroinflammatory pathways has much wider implications than targeting the primary causative pathway.
Therapeutic Targeting Of Neuroinflammation To Slow The Progression Of Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
My research has identified key components of our immune system, that can worsen disease in conditions such as Parkinson’s disease and motor neuron disease. I hope that exploring these components in animal models, and patients suffering from these diseases, my group can identify new therapeutic drug candidates that can be progressed in clinical trials. Ultimately, this may lead to new treatments to reduce disease burden in patients suffering from these neurodegenerative conditions.
Establishing The Clinical Spectrum And Pathogenicity Of Antibodies Against Dopamine Receptors In Autoimmune Movement And Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$172,126.00
Summary
Dopamine plays a pivotal role in neurotransmission and the control of movement and behaviour. This project aims to define the clinical spectrum and pathogenicity of anti-dopamine receptor antibody mediated diseases. The identification of these antibodies in atypical presentations of common movement disorders would have widespread diagnostic and therapeutic implications, and suggests that selected patients might be amenable to targeted immunomodulatory therapy, thus improving their outcome.