HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhou, Y. Articles by Kaminski, H. J. Search for Related Content PubMed PubMed Citation Articles by Zhou, Y. Articles by Kaminski, H. J.

Anti-C5 Antibody Treatment Ameliorates Weakness in Experimentally Acquired Myasthenia Gravis¹

Yuefang Zhou^*, Bendi Gong^*, Feng Lin, Russell P. Rother, M. Edward Medof^2, and Henry J. Kaminski^2,3,*

^* Department of Neurology and Psychiatry, Saint Louis University School of Medicine, St. Louis, MO 63104; Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; and Alexion Pharmaceuticals, Inc., Cheshire, CT 06410

Myasthenia gravis (MG) is a neuromuscular transmission disorder in which damage to acetylcholine receptors (AChR) on motor endplates by autoantibody-induced complement attack causes muscle weakness. To determine whether and, if so, to what extent, blockade of complement cascade at the C5 step ameliorates disease, we evaluated the effect of administering a functionally blocking anti-C5 mAb in passive experimental MG in Lewis rats induced with AChR Ab McAb-3. In contrast to uniform severe weakness at 24 h requiring euthanasia in untreated animals, anti-C5 mAb-pretreated rats showed no weakness at 48 h. Anti-C5 mAb treatment 24 h after disease induction restored strength in two-thirds of the rats. Immunofluorescence staining of endplates from the treated animals showed that C9 deposition at AChR was reduced and ultrastructural analyses showed that endplates were intact. The results argue that targeting C5 may warrant testing in MG patients and that this approach may be particularly valuable for myasthenic crisis.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R24EY014837 and R01EY013238 (to H.J.K.) and Grant P30 EY11370.

² M.E.M. and H.J.K. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Henry J. Kaminski, Department of Neurology and Psychiatry, Saint Louis University, 1438 South Grand Boulevard, St. Louis, MO 63104. E-mail address: henry.kaminski{at}tenethealth.com

⁴ Abbreviations used in this paper: MG, myasthenia gravis; AChR, acetylcholine receptor; EAMG, experimental MG; MAC, membrane attack complex.