64 91

Cited 0 times in

Integration of National Health Insurance claims data and animal models reveals fexofenadine as a promising repurposed drug for Parkinson’s disease

Authors
 Jae-Bong Kim  ;  Yujeong Kim  ;  Soo-Jeong Kim  ;  Tae-Young Ha  ;  Dong-Kyu Kim  ;  Dong Won Kim  ;  Minyoung So  ;  Seung Ho Kim  ;  Hyun Goo Woo  ;  Dukyong Yoon  ;  Sang Myun Park 
Citation
 JOURNAL OF NEUROINFLAMMATION, Vol.21(1) : 53, 2024-02 
Journal Title
JOURNAL OF NEUROINFLAMMATION
Issue Date
2024-02
MeSH
Animals ; Caenorhabditis elegans / metabolism ; Disease Models, Animal ; Dopaminergic Neurons ; Neurodegenerative Diseases* / metabolism ; Oxidopamine ; Parkinson Disease* / pathology ; Terfenadine / analogs & derivatives* ; alpha-Synuclein / metabolism
Keywords
Antihistamine ; Drug repositioning ; Fexofenadine ; Parkinson’s disease ; α-Synuclein
Abstract
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 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. 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 and the subsequent experiments suggested that fexofenadine is effective in PD via inhibition of peripheral immune cell infiltration into the brain. Conclusion: 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. © The Author(s) 2024.
Files in This Item:
T202401853.pdf Download
DOI
10.1186/s12974-024-03041-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Dukyong(윤덕용)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198842
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links