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

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.