Department of Pharmacology, Ajou University School of Medicine, 164, Worldcup-Ro, Yeongtong-Gu, Suwon, 16499, Korea.
Center for Convergence Research of Neurological Disorders, Ajou University School of Medicine, Suwon, Korea.
J Neuroinflammation. 2024 Feb 21;21(1):53. doi: 10.1186/s12974-024-03041-7.
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.
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 receptor, 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 (C. elegans) models. Finally, whole transcriptome data and Ingenuity Pathway Analysis (IPA) were used to elucidate drug mechanism pathways.
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 and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain.
Fexofenadine shows promise for the treatment of PD, identified through clinical data and validated in diverse animal models. This combined clinical and preclinical approach offers valuable insights for developing novel PD therapeutics.
帕金森病（PD）是一种常见且昂贵的进行性神经退行性疾病，其病因尚不清楚。能够直接阻止或减缓其进展的疾病修饰方法仍然是 PD 治疗中未满足的主要需求。基于临床药理学的药物再定位策略是识别治疗 PD 的新药的一种有用方法。
我们分析了从国家健康保险服务（NHIS）获得的索赔数据，该服务覆盖了韩国很大一部分人口，以在真实环境中调查抗组胺药（一类通过阻断 H1 受体治疗过敏症状的药物）与 PD 之间的关联。此外，我们使用各种 PD 动物模型（如 6-羟多巴胺（6-OHDA）、α-突触核蛋白原纤维（PFF）注射和秀丽隐杆线虫（C. elegans）模型）验证了该模型。最后，使用全转录组数据和 IPA 来阐明药物作用途径。
我们使用真实世界中的国家健康保险索赔数据确定了非索非那定是最有前途的候选药物。在包括 6-OHDA、PFF 注射和 C. elegans 模型在内的几种动物模型中，非索非那定改善了 PD 相关的病理。RNA-seq 分析和随后的实验表明，非索非那定通过抑制外周免疫细胞浸润大脑而对 PD 有效。
非索非那定通过临床数据确定并在多种动物模型中得到验证，显示出治疗 PD 的潜力。这种临床与临床前相结合的方法为开发新型 PD 治疗方法提供了有价值的见解。
