Neurodegenerative Disease Award funded by Gustof Ringstrom, Phyllis Edith Chard and Alice Margaret Jones Estate
Targeting TDP-43 to treat neurodegenerative diseases.
Dr Peter John Crouch
University of Melbourne
Co-Investigators: Dr Anthony Robert White, Dr Qiao-Xin Li, Associate Professor Kevin Jeffrey Barnham and Dr Paul Stephen Donnelly
Although neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and motor neuron disease are becoming more and more prevalent in our society, the sad reality is that effective therapeutics to treat these diseases do not exist. Our research team is trying to rectify this problem, and funding from the Brain Foundation will help us continue our research efforts.
A major obstacle in trying to develop therapeutics for neurodegenerative disease is the fact that their fundamental causes are not yet fully understood. In 2006 considerable excitement was generated when it was identified that abnormal changes to a protein known as TDP-43 are a consistent feature of different neurodegenerative diseases. This finding suggested that different neurodegenerative diseases share more in common than previously thought, but further to this, it suggested that abnormal changes to TDP-43 may be an important a causative factor in the development of neurodegeneration. Supporting this, experimental mice have been created to mimic many features of abnormal changes to TDP-43. These mice develop physical symptoms reminiscent of neurodegenerative disease in humans, including decreased cognitive capacity (i.e. decreased short-term memory) and impaired locomotive capacity (i.e. decreased ability to walk).
Our team has recently gained access to these TDP-43 mice. The focus of our current work is to use these mice to test the efficacy of compounds we have under development as potential therapeutics for neurodegenerative disease. The testing we have already completed indicates our compounds have good therapeutic outcomes. Showing their efficacy in TDP-43 mice will provide strong data to indicate whether our compounds have the potential to treat a broad range of neurodegenerative diseases.