期刊
EXPERIMENTAL NEUROLOGY
卷 225, 期 2, 页码 320-327出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2010.07.003
关键词
Acetylcholine receptor; Nanodisc; Myasthenia gravis; Immunoadsorption
资金
- NIH (National Institute of Neurologic Disorders and Stroke) [K08NS058800]
- National Institute of Allergy and Infectious Diseases [RO1 AI 058190]
- Myasthenia Gravis Foundation
- Nanodisc Inc.
Autoantibodies directed against the skeletal muscle acetylcholine receptor (AChR) play a critical role in the pathogenesis of the autoimmune disease, myasthenia gravis (MG). The pathogenic importance of anti-AChR antibodies is substantiated clinically by the often dramatic clinical improvement that follows removal of circulating antibodies utilizing extracorporeal plasma exchange (PE). Unfortunately, the effects of PE are non-specific as immunoglobulins (IgG) and other plasma proteins are removed in addition to anti-AChR IgG. In this study, we have successfully incorporated the AChR protein purified from Torpedo californicus into a Nanodisc (ND) membrane scaffold protein/phospholipid structure. We go on to demonstrate the effectiveness of this ND-AChR complex, administered intravenously, in the in vivo down-modulation of anti-AChR antibodies and subsequent amelioration of clinical disease in the experimental murine model of MG. These results provide proof-of-principle for the in vivo antigen-specific reduction of pathogenic anti-AChR antibodies utilizing ND-AChR particles. Further development of this strategy may provide an effective, antigen-specific, and readily accessible acute therapy for exacerbating MG or myasthenic crisis. (C) 2010 Elsevier Inc. All rights reserved.
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