Pedal-funded researchers receive $3.5M NCI grant

Jeff Milbrandt, MD, PhD (pictured right) and Aaron DiAntonio, MD, PhD (pictured left) received a $400,000 award from the Siteman Investment Program in 2016 for their project titled “Axonal maintenance for prevention of chemotherapy-induced peripheral neuropathy.” As cancer treatments improve, a major challenge has been ensuring that cancer survivors have the highest possible quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is a very common and often dose-limiting side effect of chemotherapy. CIPN involves damage to nerves that can trigger a self-destruction program that leads to degeneration of axons, which are the communication cables that transmit information among nerve cells. This axon degeneration can lead to numbness, tingling, and often, pain, that can persist for years after treatment. The goal of this project was to test the idea that preventing such axon degeneration would slow or block the development of CIPN. With this award, Drs. Milbrandt and DiAntonio were able to identify a number of steps in this self-destructive program, including the activation of a protein called SARM1 that is the central player in causing a damaged axon to degenerate. Furthermore, they were able to deduce that when SARM1 is genetically eliminated in an animal model, development of neuropathy is halted after chemotherapy treatment. Within the past year, Drs. Milbrandt and DiAntonio received over $3.5 million from the National Cancer Institute to continue their work in both identifying further inhibitors of axon degeneration, as well as identifying methods to block SARM1 activity to help prevent CIPN. To bring the benefits of their discovery to patients, they also started a company called Disarm Therapeutics whose goal is to identify drugs to block SARM1 activity. These inhibitors will be tested in clinical trials designed to evaluate their effectiveness in treating CIPN and other neurodegenerative disorders.

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