Chemotherapy-induced peripheral neuropathy is the most prevalent dose-limiting toxicity
caused by anti-cancer therapy and can cause permanent disability. Most chemotherapy-induced neuropathies are characterized by early nerve fiber breakdown (axonal degeneration). We developed a gene therapy strategy in mice that potently blocks axonal degeneration. To translate its benefit to the clinic, we need a means to identify patients most at risk of developing a chemotherapy-induced peripheral neuropathy and, thus, most likely to benefit from axon-protective therapy. Neurofilament light chain is a major scaffolding protein that is released by damaged axons and is a sensitive biomarker in chronic neurodegenerative diseases. In this proposal, we combine experiments in mice and evaluation of blood samples from patients treated with a high dose of the chemotherapeutic agent vincristine to determine if serum Neurofilament light chain levels can be used as a i) biomarker for acute axonal degeneration and ii) predictor of severe and/or chronic neuropathy. If successful, this study will promote future axon protective trials by objectively identifying patients most likely to benefit from axon protective therapy and provide an outcome measure for assessment of the effectiveness of the axon protective agent.