Targeting plasma cells with proteasome inhibitors: possible roles in treating myasthenia gravis?

Ann N Y Acad Sci. 2012 Dec;1274:48-59. doi: 10.1111/j.1749-6632.2012.06824.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoantibodies / metabolism
  • Boronic Acids / therapeutic use
  • Bortezomib
  • Humans
  • Myasthenia Gravis / drug therapy*
  • Plasma Cells / drug effects*
  • Plasma Cells / metabolism
  • Protease Inhibitors / therapeutic use*
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / metabolism*
  • Pyrazines / therapeutic use

Substances

  • Autoantibodies
  • Boronic Acids
  • Protease Inhibitors
  • Pyrazines
  • Bortezomib
  • Proteasome Endopeptidase Complex