Targeting Inflammatory Mechanisms In Alzheimer's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$392,750.00
Summary
Alzheimer s disease accounts for the majority of dementia cases and is the most common cause for nursing home requirements in Australia. It is not a disease that is confined to old age as it can also affect individuals in their 20s and 30s. There is currently no cure for Alzheimer's disease, largely because the underlying cause is unknown. Deposition of the amyloid-beta protein within the brain of Alzheimer's disease patients is thought to be responsible for the neuronal cell loss which underlie ....Alzheimer s disease accounts for the majority of dementia cases and is the most common cause for nursing home requirements in Australia. It is not a disease that is confined to old age as it can also affect individuals in their 20s and 30s. There is currently no cure for Alzheimer's disease, largely because the underlying cause is unknown. Deposition of the amyloid-beta protein within the brain of Alzheimer's disease patients is thought to be responsible for the neuronal cell loss which underlies the dementia. However, amyloid-beta protein deposition can occur in the absence of dementia and in the asbence of significant neuronal cell loss, suggesting that an alternative mechanism of neurotoxicity exists. Inflammation is a consistent feature of the Alzheimer's disease brain. We have preliminary evidence to suggest that inflammation is responsible for the neurotoxicity in Alzheimer's disease. We have recently observed a significant inflammatory response surrounding an unidentified protein in the brains of individuals with a familial form of Alzheimer's disease due to a genetic mutation. This inflammatory response is not associated with the significant amyloid-beta protein deposition seen in these cases suggesting that a novel potent inflammatory stimulus exists. Furthermore, these cases have greater neuronal cell loss and a shorter disease duration, both indicators of increased neurotoxicity. The present study is designed to determine the toxicity of inflammation and the stimulus driving this response in the Alzheimer's disease brain using tools for protein and gene analysis, as well as determining the extent of inflammation-mediated toxicity on neuronal cells grown in culture. Only by addressing these aims can we concentrate on developing safe and effective therapeutic strategies to prevent or treat the disease process.Read moreRead less
Functional Studies On A Neuroprotective Activity Of The Amyloid Precursor Protein Of Alzheimer S Disease.
Funder
National Health and Medical Research Council
Funding Amount
$160,475.00
Summary
Alzheimer's disease is a major health problem of the elderly. With our aging population living longer, this presents enormous economic and social pressures. Research into the mechanism of Alzheimer's disease is therefore of immediate importance. In this study we are trying to determine the relationship between proteins involved in the disease process. In particular we are studying the amyloid precursor protein (APP). APP has both therapeutic as well as disease causing actions. It gives rise to t ....Alzheimer's disease is a major health problem of the elderly. With our aging population living longer, this presents enormous economic and social pressures. Research into the mechanism of Alzheimer's disease is therefore of immediate importance. In this study we are trying to determine the relationship between proteins involved in the disease process. In particular we are studying the amyloid precursor protein (APP). APP has both therapeutic as well as disease causing actions. It gives rise to the toxic amyloid peptide Abeta which is responsible for disease. However APP can also inhibit Abeta toxicity thus controlling cell death. We are studying how APP is able to modulate the neurotoxic activity of Abeta. These studies will identify key aspects of the disease pathway and hopefully lead to treatment strategies.Read moreRead less
Pathophysiology Of Oxaliplatin-induced Nerve Dysfunction And Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$281,255.00
Summary
When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been com ....When treating patients diagnosed with cancer, nerve dysfunction is a common complication of chemotherapy, particularly with oxaliplatin. Neurological symptoms develop in up to 90% of patients following oxaliplatin treatment. Neurotoxicity is a key factor in determining the dosage and frequency of current chemotherapeutic agants. Oxaliplatin therapy results in disabling neurological effects. Onset of neuropathy can be relatively fast or in other cases may develop months after therapy has been completed. The other chief problems encountered during chemotherapy can be overcome: nausea and vomiting can be treated; myelosuppression can be reversed. End organ toxicity such as neuropathy cannot be controlled. Despite the high incidence of neuropathy due to chemotherapy, the mechanisms involved remain poorly understood, particularly with newer therapies. The aim of the present study is to measure nerve function in oncology patients treated with oxaliplatin using a novel protocol, attempting ultimately to identify aspects of dysfunction that correlate with clinical abnormalities, so helping to pin-point the mechanisms responsible for neuropathy. Once identified, management strategies can be developed to better target the prevention and treatment of neuropathy in oncology patients treated with chemotherapy.Read moreRead less
KYNURENINE PATHWAY METABOLOMIC PROFILING IN THE PROGRESSION OF MULTIPLE SCLEROSIS: DEVELOPMENT OF NOVEL BIOMARKER TO ASSESS DISEASE SEVERITY AND THERAPEUTIC REGIMEN
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
A metabolic process known as the kynurenine pathway (KP) has been found to be dysregulated in multiple sclerosis (MS) patients. We are currently investigating which components of the KP is impaired that put MS patients in jeopardy. Next, we aim to use specific drugs known to manipulate the KP in order to rectify the impairment and stop MS. Outcome of this study may potentially lead to discovery of new biomarkers to assess severity of MS progression and also novel therapeutic regimen.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
Mechanisms Of Ion Channel Dysfunction In Hereditary And Acquired Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$404,869.00
Summary
Nerve function is dependent on ion channels, which provide the basis for neurotransmission. Inherited or acquired abnormalities in ion channel function are important in diseases including epilepsy, pain disorders, neuromuscular diseases and toxic neuropathy. This project will use a combination of techniques to study mechanisms underlying nerve dysfunction to compare genetic nerve problems and acquired nerve damage to understand how damage occurs and develop new therapies and diagnostic tests.