$125,000 awarded to Dr. Marco Prado, Western University with co-investigators Dr. Martin Duennwald and Dr. Flavio Beraldo, Western University.
Increased levels and clumping of the protein TDP-43 occur in more than 95% of ALS cases, making it an attractive target for understanding what causes the disease and finding new ways to treat it. In normal cells, a set of proteins called heat shock proteins may act as guardians to defend against TDP-43 toxicity. Dr. Prado and colleagues have demonstrated that the amount of a heat shock protein called STI1 is lower in ALS motor neurons compared to healthy motor neurons and that these lower levels directly affect the toxicity of abnormal TDP-43. In this project, they will study mice with abnormal TDP-43 and determine whether increasing or decreasing STI1 levels can preserve motor neuron health. Understanding this mechanism of action may shed light on future potential avenues for treatment. This project could also provide the first evidence that STI1 itself might be a valuable target to test in human clinical trials.