Combined Therapeutic Approach: Inhibition of MMP-9 and JAK Signaling Synergistically Prevents Depigmentation in Experimental Vitiligo

The study investigates a combined therapeutic approach to prevent depigmentation in vitiligo by inhibiting MMP-9 and JAK signaling. Using both in vitro and in vivo models, researchers found that the selective MMP-9 inhibitor, JNJ0699, significantly reduced melanocyte detachment and inflammatory chemokine upregulation caused by cytokines IFN-γ and TNF-α. In a murine model, topical application of MMP9i prevented depigmentation, and when combined with ruxolitinib cream, a JAK1/2 inhibitor, it offered enhanced protection against melanocyte loss. The findings suggest that this combination therapy could preserve melanocyte adhesion and integrity, providing a promising strategy for durable clinical benefits in vitiligo treatment.