| Autor: |
Shevtsov A; Institute of Bioengineering, Research Center of Biotechnology, Russian Academy of Science, 117312 Moscow, Russia., Raevskiy M; École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.; I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia., Stupnikov A; Department of Biomedical Physics, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia.; The National Medical Research Center for Endocrinology, 117036 Moscow, Russia., Medvedeva Y; Institute of Bioengineering, Research Center of Biotechnology, Russian Academy of Science, 117312 Moscow, Russia.; Department of Biomedical Physics, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia.; The National Medical Research Center for Endocrinology, 117036 Moscow, Russia. |
| Abstrakt: |
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. |
