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bioRxiv · 10.1101/2025.07.22.666225

Integrated Multi-omics Prioritizes Ribosomal-targeting Omacetaxine Mepesuccinate for Optic Neuritis Therapy

Zhang, Y.·Huang, y.·Guo, M.
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Abstract

BackgroundOptic neuritis (ON), an acute demyelinating disorder often preceding multiple sclerosis, lacks therapies preventing neurodegeneration despite corticosteroid use. MethodsWe combined GWAS (FinnGen cohort, finn-b-H7_OPTNEURITIS), immune-specific eQTL analysis (CAGE.sparse microglia/astrocytes), and network pharmacology. SMR-HEIDI filtering (p_HEIDI>0.05; FDR<0.05) validated causal genes. Results46 ON-associated genes identified, with HLA-DRB1 as top risk locus (OR=3.297, FDR<0.01).Functional enrichment revealed antigen presentation dysregulation (GO:0002483, FDR=0.0025) and phagosome activation (hsa04145, FDR=0.0468), confirming microglial-astrocytic pathology.Omacetaxine mepesuccinate prioritized as sole repurposing candidate (FDR=0.0467) targeting ribosomal proteins RPL3/RPL2--mechanistically linked to glial protein synthesis suppression in demyelination. ConclusionsThis first multi-omics analysis of ON bridges HLA-mediated autoimmunity with repurposed ribosomal-targeted therapy, proposing omacetaxine for neuroprotection.

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Zhang, Y., Huang, y., Guo, M.. 2025-07-26. Integrated Multi-omics Prioritizes Ribosomal-targeting Omacetaxine Mepesuccinate for Optic Neuritis Therapy. https://doi.org/10.1101/2025.07.22.666225

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