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Proteasome inhibitor ups survival of mice with lupus
Last Updated: 2008-06-09 15:07:17 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Treatment with the proteasome inhibitor bortezomib, an approved agent for multiple myeloma, can improve glomerulonephritis and prolong survival in mice with lupus-like disease, according to a report in the June 8th online issue of Nature Medicine.
Systemic lupus erythematosus and other autoimmune diseases can be difficult to treat because the plasma cells that produce the disease-causing antibodies are long-lived and resistant to current therapies, note senior author Dr. Reinhard E. Voll, from the University Hospital Erlangen in Germany, and colleagues.
In an earlier study, the researchers had shown that the degree to which bortezomib reduces myeloma cells is directly related to how much antibody the cells produce. Thus, they hypothesized that normal, but high-antibody-producing plasma cells, which are found with lupus, may also be particularly sensitive to the drug.
In the current investigation, bortezomib eliminated both short- and long-lived plasma cells by activating the terminal unfolded protein response. In murine models of lupus, the drug eliminated autoantibody production, attenuated nephritis and improved survival.
"The elimination of autoreactive plasma cells by proteasome inhibitors might represent a new treatment strategy for antibody-mediated diseases," the investigators conclude.
Nat Med 2008.
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