Dynavax Technologies has reported that its proprietary IRS 954, a specific inhibitor of two toll-like receptors TLR7 and TLR9, can prevent progression of disease when injected in lupus-prone F1 mice.
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In tests, the treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 led to reduction of autoantibody production and amelioration of disease symptoms.
A significant reduction of serum levels of nucleic acid specific autoantibodies, the hallmark of systemic lupus erythematosus, was also observed. IRS 954 treatment also resulted in decreased proteinuria, glomerulonephritis and end-organ damage, and increased survival, compared to untreated mice.
IRS 954 represents a novel class of oligonucleotides, named immunoregulatory sequences (IRS), that specifically inhibit the TLR-induced inflammatory response implicated in disease progression in lupus.
Robert Coffman, vice president and chief scientific officer of Dynavax, said: “These results show that the previously reported ability of IRS 954 to block IFN-alpha translates into reduced symptoms in an animal model of lupus. The data support our hypothesis that blocking both TLR7 and TLR9 in B cells and in human plasmacytoid dendritic cells is a promising new approach for the treatment of lupus.”
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