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

## TL;DR

The study shows that mebendazole, a drug typically used for worms, may help treat systemic lupus erythematosus in mice by improving disease symptoms.

## Contribution

The study demonstrates mebendazole's therapeutic potential in a spontaneous lupus model through both preventive and therapeutic efficacy.

## Key findings

- Mebendazole reduced proteinuria and anti-dsDNA antibodies in NZBxNZWF1 mice.
- The drug also decreased glomerular IgG deposition in both preventive and therapeutic settings.
- Exploratory data suggest mebendazole may influence ERK signaling in B cells.

## Abstract

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.