Integration of National Health Insurance Claim Data and Animal Models Reveals Fexofenadine as a Promising Repurposed Drug for Parkinson’s Disease

Background: Parkinson’s disease (PD) is a common and costly progressive neurodegenerative disease of unclear etiology. A disease-modifying approach that can directly stop or slow its progression remains a major unmet need in the treatment of PD. A clinical pharmacology-based drug repositioning strategy is a useful approach for identifying new drugs for PD. Methods We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion of the South Korean population, to investigate the association between antihistamines, a class of drugs commonly used to treat allergic symptoms by blocking H1 receptors, and PD in a real-world setting. Additionally, we validated this model using various animal models of PD such as the 6-hydroxydopmaine (6-OHDA), α-synuclein preformed fibrils (PFF) injection, and Caenorhabditis elegans models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways. Results We identified fexofenadine as the most promising candidate using National Health Insurance claims data in the real world. In several animal models, including the 6-OHDA, PFF injection, and C. elegans models, fexofenadine ameliorated PD-related pathologies. RNA-seq analysis suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. Conclusion This approach, which combines National Health Insurance claims data and animal model systems, provides insights into the development of novel therapeutics for PD.