Dataset Information

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

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.

SUBMITTER: Kim JB

PROVIDER: S-EPMC10880337 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Kim Jae-Bong JB Kim Yujeong Y Kim Soo-Jeong SJ Ha Tae-Young TY Kim Dong-Kyu DK Kim Dong Won DW So Minyoung M Kim Seung Ho SH Woo Hyun Goo HG Yoon Dukyong D Park Sang Myun SM

Journal of neuroinflammation 20240221 1

<h4>Background</h4>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.<h4>Methods</h4>We analyzed claims data obtained from the National Health Insurance Service (NHIS), which covers a significant portion ...[more]

PMID: 38383441

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Project description:Objective To measure incidence of early death after discharge from emergency departments, and explore potential sources of variation in risk by measurable aspects of hospitals and patients.Design Retrospective cohort study.Setting Claims data from the US Medicare program, covering visits to an emergency department, 2007-12.Participants Nationally representative 20% sample of Medicare fee for service beneficiaries. As the focus was on generally healthy people living in the community, patients in nursing facilities, aged ≥90, receiving palliative or hospice care, or with a diagnosis of a life limiting illnesses, either during emergency department visits (for example, myocardial infarction) or in the year before (for example, malignancy) were excluded.Main outcome measure Death within seven days after discharge from the emergency department, excluding patients transferred or admitted as inpatients.Results Among discharged patients, 0.12% (12 375/10 093 678, in the 20% sample over 2007-12) died within seven days, or 10 093 per year nationally. Mean age at death was 69. Leading causes of death on death certificates were atherosclerotic heart disease (13.6%), myocardial infarction (10.3%), and chronic obstructive pulmonary disease (9.6%). Some 2.3% died of narcotic overdose, largely after visits for musculoskeletal problems. Hospitals in the lowest fifth of rates of inpatient admission from the emergency department had the highest rates of early death (0.27%)-3.4 times higher than hospitals in the highest fifth (0.08%)-despite the fact that hospitals with low admission rates served healthier populations, as measured by overall seven day mortality among all comers to the emergency department. Small increases in admission rate were linked to large decreases in risk. In multivariate analysis, emergency departments that saw higher volumes of patients (odds ratio 0.84, 95% confidence interval 0.81 to 0.86) and those with higher charges for visits (0.75, 0.74 to 0.77) had significantly fewer deaths. Certain diagnoses were more common among early deaths compared with other emergency department visits: altered mental status (risk ratio 4.4, 95% confidence interval 3.8 to 5.1), dyspnea (3.1, 2.9 to 3.4), and malaise/fatigue (3.0, 2.9 to 3.7).Conclusions Every year, a substantial number of Medicare beneficiaries die soon after discharge from emergency departments, despite no diagnosis of a life limiting illnesses recorded in their claims. Further research is needed to explore whether these deaths were preventable.

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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