In Silico Drug Repurposing in Multiple Sclerosis Using scRNA-Seq Data

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system still lacking a cure. Treatment typically focuses on slowing the progression and managing MS symptoms. Single-cell transcriptomics allows the investigation of the immune system-the key player in MS onset and development-i...

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Veröffentlicht in:International journal of molecular sciences 2023-01, Vol.24 (2), p.985
Hauptverfasser: Shevtsov, Andrey, Raevskiy, Mikhail, Stupnikov, Alexey, Medvedeva, Yulia
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Sprache:eng
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Zusammenfassung:Multiple sclerosis (MS) is an autoimmune disease of the central nervous system still lacking a cure. Treatment typically focuses on slowing the progression and managing MS symptoms. Single-cell transcriptomics allows the investigation of the immune system-the key player in MS onset and development-in great detail increasing our understanding of MS mechanisms and stimulating the discovery of the targets for potential therapies. Still, de novo drug development takes decades; however, this can be reduced by drug repositioning. A promising approach is to select potential drugs based on activated or inhibited genes and pathways. In this study, we explored the public single-cell RNA data from an experiment with six patients on single-cell RNA peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid cells (CSF) of patients with MS and idiopathic intracranial hypertension. We demonstrate that AIM2 inflammasome, SMAD2/3 signaling, and complement activation pathways are activated in MS in different CSF and PBMC immune cells. Using genes from top-activated pathways, we detected several promising small molecules to reverse MS immune cells' transcriptomic signatures, including AG14361, FGIN-1-27, CA-074, ARP 101, Flunisolide, and JAK3 Inhibitor VI. Among these molecules, we also detected an FDA-approved MS drug Mitoxantrone, supporting the reliability of our approach.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24020985