June 17, 2010
Dynavax Technologies Corporation (NASDAQ: DVAX) today reported in NATURE new data that may explain the resistance of lupus patients to glucocorticoid treatment. In the June 16, 2010 issue of NATURE, Dynavax scientists show that activation of cells of the innate immune system by two key receptors, TLR7 and TLR9, can cause glucocorticoid resistance in lupus patients. The data also demonstrate that this resistance can be reversed by Dynavax's novel TLR7/TLR9 inhibitors in human blood cells and animal models of lupus.
Glucocorticoids are widely used for the treatment of many autoimmune and inflammatory conditions, but the high doses required for effective treatment of lupus lead to significant side-effects. In the article entitled, "TLR Recognition of Self Nucleic Acids Hampers Glucocorticoid Activity in Lupus," researchers from Dynavax and their collaborators show that patients' own RNA and DNA can cause a key cell type to become resistant to the killing effects of glucocorticoids. This response to self RNA and DNA operates via two key receptors, TLR7 and TLR9, which are the targets of a novel inhibitory drug being developed by Dynavax.
"Our findings reveal a novel potential for TLR inhibitors to permit effective glucocorticoid therapy with lower, better-tolerated doses," commented Robert Coffman, Ph.D., Chief Scientific Officer of Dynavax. "There is an urgent need for new therapies for lupus and we look forward to advancing our lead TLR inhibitor, DV1179, into clinical trials later this year."
This work was conducted in collaboration with investigators at the Baylor Institute for Immunology Research, the Texas Scottish Rite Hospital and the University of Texas Southwestern Medical Center, all in Dallas, TX; the National Institutes of Health in Bethesda, MD; and the Institut Curie in Paris, France. The research was supported in part by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases, the Alliance for Lupus Research and the Mary Kirkland Center for Lupus Research.