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Transcriptomics- and Genomics-Guided Drug Repurposing for the Treatment of Vesicular Hand Eczema Publisher



Rosenberg FM1 ; Kamali Z2, 3 ; Voorberg AN1 ; Oude Munnink TH4 ; Van Der Most PJ2 ; Snieder H2 ; Vaez A2, 3 ; Schuttelaar MLA1
Authors
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Authors Affiliations
  1. 1. Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, Netherlands
  2. 2. Department of Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen, 9713 GZ, Netherlands
  3. 3. Department of Bioinformatics, School of Advanced Medical Technologies, Isfahan University of Medical Sciences, P.O. Box 81746-7346, Isfahan, Iran
  4. 4. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, Netherlands

Source: Pharmaceutics Published:2024


Abstract

Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe chronic HE. This emphasizes the need for alternative treatment approaches. Therefore, our study aimed to identify drug repurposing opportunities for VHE using transcriptomics and genomics data. We constructed a gene network by combining 52 differentially expressed genes (DEGs) from a VHE transcriptomics study with 3 quantitative trait locus (QTL) genes associated with HE. Through network analysis, clustering, and functional enrichment analyses, we investigated the underlying biological mechanisms of this network. Next, we leveraged drug–gene interactions and retrieved pharmaco-transcriptomics data from the DrugBank database to identify drug repurposing opportunities for (V)HE. We developed a drug ranking system, primarily based on efficacy, safety, and practical and pricing factors, to select the most promising drug repurposing candidates. Our results revealed that the (V)HE network comprised 78 genes that yielded several biological pathways underlying the disease. The drug–gene interaction search together with pharmaco-transcriptomics lookups revealed 123 unique drug repurposing opportunities. Based on our drug ranking system, our study identified the most promising drug repurposing opportunities (e.g., vitamin D analogues, retinoids, and immunomodulating drugs) that might be effective in treating (V)HE. © 2024 by the authors.
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