109. Pifithrin-μ prevents paclitaxel-induced peripheral neuropathy in a mouse model

Chemotherapy-induced peripheral neuropathy (CIPN) occurs in about 60% of cancer patients undergoing treatment. With no FDA-approved drugs to treat CIPN, a significant number of patients receive sub-optimal anti-cancer treatment. Damage to mitochondria in peripheral sensory neurons contributes to mechanical hyperalgesia in rodent models of CIPN. In this study we investigated if a mitochondrial protectant, Pifithrin-μ (PFT-μ), prevented CIPN both during and after completion of chemotherapy. In mice treated with paclitaxel alone increased hyperalgesia was present both during and after completion of chemotherapy. In mice treated with PFT-μ systemically (intraperitoneal-i.p) alone or in combination with paclitaxel, mechanical hyperalgesia was not measured both during and after completion of chemotherapy. Administration of PFT-μ intrathecally (i.t.) was also protective against CIPN, with no measurement of hyperalgesia throughout treatment. These data demonstrate that administration of PFT-μ (i.p. or i.t.) prevents CIPN. One of the potential risks of treating CIPN with PFT-μ is that it may interfere with cancer treatment. To investigate this we co-cultured human ovarian tumor cells with paclitaxel alone or in combination with PFT-μ. Significant paclitaxel-induced tumor cell death was measured when tumor cells were cultured with paclitaxel alone or in combination with PFT-μ. These data demonstrate that PFT-μ does not interfere with paclitaxel-induced tumor cell death. This study found that PFT-μ is a potential therapeutic for preventing CIPN thereby improving quality of life in cancer survivors.