Treatment of Multiple Sclerosis with Small Molecule IL-6/STAT3 Inhibitors
Small-molecule prodrugs that target IL-6/STAT3 signaling pathway.
Multiple Sclerosis (MS), an unpredictable and disabling autoimmune disease affecting the central nervous system, is the leading cause of non-traumatic neurological disability in young adults. There have been important advances in MS therapy, such as drugs that slow the progression of the disease and reduce attacks, but current treatments are only partially effective and new, innovative strategies are still needed. MS has an array of symptoms and unique characteristics that make traditional drug therapy difficult; new and innovative therapies that target a common element to multiple pathways of MS pathogenesis would provide a significant improvement over current strategies that target a single pathway. One potential pathway of interest is IL-6/STAT3, as dysregulation of IL-6 signaling plays a significant role in the pathogenesis of MS and other autoimmune diseases.
Researchers at The Ohio State University, led by Drs. Chenglong Li and Yuhong Yang, have developed small-molecule prodrugs that target the IL-6/STAT3 pathway, which is common to multiple pathogenic pathways in MS. They have developed several inhibitor analogs and have shown that these analogs suppress production of inflammatory cytokines in vitro and in vivo. The compounds have been shown to suppress pSTAT3 expression and IL-17 production in myelin-specific CD4 T cells in a dose-dependent manner. When tested in vivo, the analogs were able to suppress disease development in a chronic EAE model of MS in vivo.