Histone Inhibitor Slows Lupus Nephritis In Mice

NEW YORK (Reuters Health) - Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, lessens lupus-related kidney disease progression in a murine model, researchers report in the September 15th issue of the Journal of Immunology.

Lead investigator Dr. Christopher M. Reilly told Reuters Health that "we have been investigating the role of histone deacetylase inhibitors...for the treatment of lupus nephritis for several years. Our studies have shown beneficial effects in two lupus mouse models."

In the current study, Dr. Reilly, of Virginia Polytechnic Institute and State University, Blacksburg, and colleagues found that SAHA inhibited production of inflammatory mediators including TNF-alpha and interleukin 6 in mesangial cells -- the principal resident immmunoregulatory cells in the kidney -- from MRL/lpr mice.

Moreover, daily SAHA injections given to MRL/Lpr mice decreased spleen size and decreased renal pathology scores. Serum antibody levels and glomerular IgC and C3 deposition in these animals were similar to those in controls.

Dr. Reilly noted that SAHA is currently in clinical trials for the treatment of specific cancers. He and his colleagues, he added, are now "in the process of completing the necessary steps to begin early clinical trials in humans to determine if SAHA will have the same beneficial effects that we have seen in mice."

Source: J Immunol 2004;173. [ Google search on this article ]

MeSH Headings: Histones : Nuclear Proteins