Journal
MYASTHENIA GRAVIS AND RELATED DISORDERS I
Volume 1274, Issue -, Pages 48-59Publisher
BLACKWELL SCIENCE PUBL
DOI: 10.1111/j.1749-6632.2012.06824.x
Keywords
bortezomib; plasma cell; myasthenia gravis; proteasome inhibition; autoimmunity
Categories
Funding
- European Union
- Prinses Beatrix Fonds [WAR08-12]
- Association Francaise contre les Myopathies
- Genmab
- UK Medical Research Council
- Netherlands Organization for Scientific Research
- Brain Foundation of the Netherlands
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Myasthenia gravis (MG) is treated primarily with broad-spectrum immuno-suppressants such as prednisone or azathioprine, which normally require several months to reduce autoantibody titers significantly. This delay may be caused by the resistance of the main antibody-producing cells, the plasma cells, to these drugs. In particular, long-lived plasma cells are resistant to immunosuppressive treatments and can produce (auto-) antibodies for months. Bortezomib is a proteasome inhibitor approved for treating patients with multiple myeloma, a plasma cell malignancy. Recent preclinical studies in cell cultures and animal models, and clinical studies in organ-transplant recipients, have demonstrated that bortezomib can kill non-neoplastic plasma cells within hours. This suggests that proteasome inhibitors could also be used for rapidly reducing autoantibody production in autoimmune diseases. We have begun to assess their potential in MG.
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