Mobilizing stem cells and inhibition of autoimmunity synergistically modify autoimmune disease to relieve pain: a potential MRG-001 therapy for rheumatoid arthritis.

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, bone erosion, cartilage destruction, and debilitating pain. Current therapies often fall short in preventing structural damage and restoring immune balance. To address these limitations, we evaluated MRG-001 - a fixed-dose combination of plerixafor (AMD3100) and low-dose tacrolimus (FK506) with reported immunoregulatory and regenerative potential - in preclinical models of RA. Methods: The therapeutic efficacy of MRG-001 was assessed in collagen-induced arthritis and collagen antibody-induced arthritis mouse models. Mice received subcutaneous MRG-001, and clinical, histological, molecular, and behavioral endpoints were evaluated to examine inflammation, immune modulation, bone integrity, angiogenesis, and pain. Results: MRG-001 treatment significantly reduced joint swelling, arthritis scores, and pro-inflammatory cytokine expression (TNF-α, IL-6, IL-17a) in both models. It was associated with mobilization of CD45 Conclusions: MRG-001 exerts broad therapeutic effects in RA by modulating immune responses, preserving joint architecture, and alleviating pain. These findings support its potential as a novel, multi-modal disease-modifying therapy for RA and warrant further clinical investigation.