Use of Inhibitors of TLR-7, 8 and 9–Induced IFN-alpha for the Treatment of Lupus
Barrat, Franck, PhD
Dynavax Technologies, Inc.
Interferon-alpha (IFN-alpha) is a substance normally involved in the immune response to viral infections. Research indicates that people with SLE have abnormally elevated serum levels of IFN-alpha that correlate with disease severity. Although the cause of this increase is still not fully understood, growing evidence links IFN-alpha production with the activation of a rare type of immune cell in the blood—the plasmacytoid dendritic cells (PDCs). Recent studies suggest that clusters of autoantibodies and molecules from the body’s own cells, known as immune complexes, can trigger IFN-alpha production in much the same way as a virus does, through the activation of specific receptors known as Toll-like receptors (TLRs). Dr. Barrat and his colleagues believe that interfering with the activation of PDCs by these Toll-like receptors will reduce the amount of IFNalpha in the circulation and therefore reduce symptoms of lupus. The goal of this project is to evaluate a novel class of Toll-like receptor inhibitors composed of short pieces of DNA that block IFN-alpha production in PDCs by both viruses and immune complexes. Dr. Barrat and his colleagues will do experiments to better understand how these new TLR inhibitors work and how they might be used to treat lupus, including studies in mice with lupus-like disease.
What this study means for people with lupus: Decreasing IFN-alpha levels in SLE patients is predicted to reduce the symptoms of the disease. By specifically inhibiting the cells that produce IFN-alpha in response to either viruses or immune complexes, the approach being evaluated by Dr. Barrat could lead to a new and more specific treatment for lupus.