Background: Oxaliplatin causes oxaliplatin-induced peripheral neuropathy (OIPN). Because OIPN reduces patients' quality of life (QOL), the development of preventive agents against OIPN is an important area of research. In this study, we searched for preventive drugs against OIPN by drug repositioning, using large-scale medical data, and experimentally validated the findings with neuron-like cells and OIPN rat models.
Methods and Results: First, we searched for approved drugs that cancel the gene expression change caused by oxaliplatin, using the drug discovery tool LINCS, and found 23 approved drugs that met the requirements. Candidate drugs were then evaluated for their mitigating effects on OIPN, using the FDA Adverse Event Reporting System (FAERS) database, and Drug X was found to significantly reduce the risk of patients developing OIPN. Using PC12 cells, we observed significant improvement in oxaliplatin-associated axonal damage with Drug X treatment. In addition, in vivo experiments showed that Drug X significantly reduced the expression of oxaliplatin-induced neuropathy in OIPN rat models.
Conclusion: This study suggested that drug repositioning of Drug X could allow it to be used as a preventive agent for OIPN.