Efficacy of mebendazole in the spontaneous NZBxNZWF1 animal model of systemic lupus erythematosus.

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Eloranta ML, Nygren P, Larsson R, Loskog A, Woodworth N, Hultqvist M, Svensson R, Gravenfors Y, Rönnblom L, Fryknäs M

Sci Rep 16 (1) 6357 [2026-02-12; online 2026-02-12]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex etiology involving both innate and adaptive immune dysregulation. Among several perturbed signaling pathways, decreased ERK activity in CD4⁺ T-cells has been linked to DNA hypomethylation and aberrant gene expression in SLE. Mebendazole (MBZ), an anti-helminthic drug with a well-established safety profile, has shown immunomodulatory effects in preclinical studies, including activation of the MEK/ERK pathway and inhibition of MAPK14 (p38), a known driver of inflammation. To evaluate the therapeutic potential of MBZ in SLE, we tested its efficacy in NZBxNZWF1 mice, a spontaneous and well-characterized SLE model. MBZ treatment resulted in reduced proteinuria, lower anti-dsDNA antibody levels, and diminished glomerular IgG deposition, both in preventive and therapeutic settings. Exploratory in vitro data suggest that MBZ may also influence ERK signaling in B cells, while the mechanistic basis of these effects remains to be clarified. Our findings demonstrate robust phenotypic improvements and support further investigation of MBZ as a repositioned candidate for SLE. The online version contains supplementary material available at 10.1038/s41598-026-37930-z.

Drug Discovery and Development [Service]

PubMed 41680254

DOI 10.1038/s41598-026-37930-z

Crossref 10.1038/s41598-026-37930-z

pmc: PMC12905218
pii: 10.1038/s41598-026-37930-z