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Therapeutic targeting of neuroinflammation to slow the progression of neurodegenerative disease (2016–2020)

Abstract:
Neurodegenerative diseases remain a major burden on society. There are no effective treatments for these conditions, and as the population ages, these diseases are on the rise. Thus, there is an urgent need to further understand the mechanisms underlying these conditions, and test new therapies, in order to advance new drugs into the clinic. Neuroinflammation is emerging as a key, and relevant process that contributes to the death of neurons in neurodegenerative disease. My laboratory has demonstrated that components of the innate immune system (eg. complement, toll-like receptors, and inflammasomes) are active in the brain, and contribute to neuroinflammatory processes during neurodegeneration. Specific targeting of these pathways using novel drugs developed by my group, can slow disease progression in models of these diseases. The overall goal of my proposed fellowship is to further explore these innate immune pathways in these diseases, using both cellular and animal models, as well as examining clinical material in human patients. My hypothesis is that innate immune-mediated neuroinflammation is a key contributor to the underlying pathology of neurodegenerative disease, and that therapeutic targeting of specific innate molecules can reduce disease progression. I will investigate three major aims: 1: To further understand the mechanisms underlying neuroprotection following blockade of inflammation in neurodegenerative diseases. 2: To identify new therapeutic targets and develop novel drugs to target inflammation in neurodegenerative disease. 3: To validate therapeutic targets in human patients by working closely with neurologists, on the ultimate road to clinical translation. Overall, it is my hope that further research into this area will identify new, and progress existing therapeutics into clinical trials. This may lead to new therapies that cou...
Grant type:
NHMRC Career Development Fellowship
Researchers:
Funded by:
National Health and Medical Research Council