Analyzing the efficacy of MMP-13 inhibitors in the treatment of CIPN

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Project Summary The goal of this project is to establish an effective drug candidate to treat chemotherapy-induced peripheral neuropathy (CIPN). The National Cancer Institute estimates that approximately 400,000 (or ~60-70%) of patients undergoing chemotherapy suffer from CIPN. These patients may need to terminate chemotherapy treatment if experiencing symptoms, such as numbness, pain, temperature sensitivity, or tingling. Cancer survivors furthermore often have to live with CIPN for the rest of their lives. To date are no treatments available with which to tackle this problem. CIPN costs the healthcare system upward of $13B annually for long-term care of the patients. Thus, there is a significant clinical and economical need to develop drug therapies. Avantyx Pharmaceuticals, LLC has identified a new compound targeting the Matrix-Metalloproteinase 13 (MMP-13), which was shown to promote the degeneration of sensory nerve endings in animal models for CIPN induced by paclitaxel treatment. The key focus of this Phase I project is to characterize a novel MMP-13 inhibitor for its bioavailability, efficacy, specificity, and toxicity in a rat model of paclitaxel-induced peripheral neuropathy, which is following studies in which we established the efficacy of this inhibitor in zebrafish. Key goals are to establish parameters, such as optimal route of administration (oral or topical), optimal dosing, and target specificity, which is necessary to proceed to further drug development studies in Phase II.