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Author Spotlight: Novel Assay for Studying B-Cell Responses in Multiple Sclerosis Research
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Immune cells transcriptome-based drug repositioning for multiple sclerosis.

Xinyue Yin1, Xinming Rang1, Xiangxiang Hong1

  • 1Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Frontiers in Immunology
|November 7, 2022
PubMed
Summary

This study identifies potential new uses for existing drugs to treat multiple sclerosis (MS) by analyzing gene expression data. Candidate drugs targeting key pathways like PI3K-Akt and Chemokine signaling show promise for MS treatment.

Keywords:
candidate drugdifferentially expressed genedrug repositioningmultiple sclerosistranscriptome

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Area of Science:

  • Immunology
  • Pharmacology
  • Bioinformatics

Background:

  • Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
  • Identifying novel therapeutic strategies for MS is crucial, with drug repositioning offering a promising avenue.

Purpose of the Study:

  • To identify existing drugs that can be repurposed for multiple sclerosis (MS) treatment.
  • To find target genes and pathways in MS immune cells based on transcriptomic changes.

Main Methods:

  • Transcriptome data from the Gene Expression Omnibus (GEO) database was analyzed.
  • Bioinformatics approaches, including protein-protein interaction networks and the Connectivity Map (CMap) database, were used to identify hub genes and candidate drugs.
  • Kyoto Encyclopedia of Genes and Genomes (KEGG) database was utilized to determine target pathways.

Main Results:

  • Several hub target genes were identified for CD4+ T cells (Fingolimod) and Plasmacytoid dendritic cells (pDCs)/Peripheral blood mononuclear cells (PBMC) (interferon-β).
  • Six candidate drugs targeting multiple hub genes and 69 candidate drugs targeting multiple pathways were identified.
  • Key pathways identified include immune system and viral infectious disease pathways.

Conclusions:

  • Candidate drugs targeting the PI3K-Akt and Chemokine signaling pathways, such as Nemiralisib and Umbralisib, may be effective for MS treatment.
  • Tyrosine kinase inhibitors like Fostamatinib represent potential therapeutic options for multiple sclerosis.