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
A Multi-site RCT Comparing Spinal And General Anaesthesia On Neurodevelopmental Outcome And Apnoea In Infants
Funder
National Health and Medical Research Council
Funding Amount
$512,072.00
Summary
5% of Australian children have surgery when they are infants. Recent studies have shown that surgery in babies is associated with poorer neurological outcomes. The reason for this is unclear but animal experiments suggest it may be due to some anaesthetic agents. This trial will determine if the anaesthetic is the cause of the problem. 660 babies who need surgery will be randomised to receive a general or local anaesthetic, and then followed for 5 years.
NOVEL THERAPIES FOR ALZHEIMER'S DISEASE BASED ON A-BETA - METAL INTERACTIONS
Funder
National Health and Medical Research Council
Funding Amount
$461,443.00
Summary
The genetic data clearly show that the amyloid protein (A-beta) is central to the brain damage which occurs in Alzheimer's disease (AD). However exogenous or environmental factors involved in regulating its toxic actions are not understood. We have shown that the metals zinc and copper have dramatic effects on the properties of A-beta and that chemicals which alter the amounts of these metals in the brain may be useful in treating the disease. In this project we are investigating the ability of ....The genetic data clearly show that the amyloid protein (A-beta) is central to the brain damage which occurs in Alzheimer's disease (AD). However exogenous or environmental factors involved in regulating its toxic actions are not understood. We have shown that the metals zinc and copper have dramatic effects on the properties of A-beta and that chemicals which alter the amounts of these metals in the brain may be useful in treating the disease. In this project we are investigating the ability of one such compound to affect the metabolism of A-beta in a mouse model of AD.Read moreRead less