This $419,474 project grant from the National Cancer Institute, part of the Department of Health and Human Services, supports research under the Cancer Treatment Research program to develop mechanism-based strategies to treat chemotherapy-induced peripheral neuropathy. The awardee, Washington University, will utilize a SARM1 dominant-negative construct and virus-mediated overexpression of NAD+ salvage pathway enzymes to block the axon degeneration pathway activated by chemotherapeutic agents like vincristine and bortezomib. This final common pathway is mediated by the neuronal protein SARM1 and results in local NAD+ depletion and metabolic collapse. The research will assess the effects of these therapeutic strategies on axon degeneration, neuroinflammation, and functional outcomes in mouse models. It will also evaluate any interaction with cancer or chemotherapy in cancer-bearing mice. Success could lead directly to clinically viable means to prevent and treat this common and debilitating side effect of chemotherapy.
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