Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Myasthenia Gravis and Related Disorders REVIEW Acetylcholine receptor antibody–mediated animal models of myasthenia gravis and the role of complement Linda L. Kusner, 1 Manjistha Sengupta, 2 and Henry J. Kaminski 2 1 Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC. 2 Department of Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC Address for correspondence: Linda L. Kusner, Ph.D., Department of Pharmacology and Physiology, George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC 20037. lkusner@gwu.edu Because of the failure of many promising therapeutics identified in preclinical evaluation, funding sources have established guidelines for increased rigor in animal evaluations. The myasthenia gravis (MG) community of scientists has developed guidelines for preclinical assessment for potential MG treatments. Here, we provide a focused summary of these recommendations and the role of complement in disease development in experimental models of MG. Keywords: myasthenia gravis; passive transfer myasthenia gravis; experimental autoimmune myasthenia gravis; complement Introduction Drug development has a poor record of success for moving novel agents from ideas to actual therapies, and much of the blame lies with the inability to translate promising results from animal investiga- tions into positive results in humans. This bleak situation has led to a call to improve the rigor of preclinical evaluation of therapeutics, 1–4 with the leadership of the National Institutes of Neurological Disorders and Stroke recommending specific docu- mentation in publications of four specific areas: (1) study design requiring specific detail to assess effi- cacy, including randomization to reduce bias; (2) readout parameters in animal models that allow clear determination of disease manifestations and severity and allow determination of efficacy with evaluations being done in a blinded fashion; (3) a priori power analysis performed to justify animal number; and (4) an increasingly appreciated need for inclusion of female and male animals to assess for gender bias in therapeutic efficacy assessments. 5 Since the 2012 New York Academy of Sciences meeting dedicated to myasthenia gravis (MG) and related disorders, the community of MG scientists has faced this challenge head on at a time when biotech and large pharmaceutical company inter- est in MG is at an all-time high. In 2014, the National Institute of Neurological Disorders and Stroke and the Myasthenia Gravis Foundation of America sponsored the workshop “Standards of Pre-clinical Efficacy in Experimental Myasthenia Gravis.” The event brought together leaders in the field of animal evaluation for MG and external experts to initiate the process of developing inter- nationally accepted guidelines for preclinical exper- imental design. The goal of the conference was to produce standard operating procedures for animal models of MG that encompass the induction of the disease, longitudinal assessment measurements, and terminal evaluations to determine efficacy. Through discussion and consensus building during and after the conference, a summary of recommendations for preclinical evaluations has been published. 6 Here, we briefly review key aspects of acetylcholine recep- tor (AChR) antibody models of MG and the role of complement in driving the pathology. Passive transfer myasthenia gravis Passive transfer MG (PTMG) is produced by administration of autoantibodies directed toward the AChR and more recently the muscle- specific kinase (MuSK) and low-density lipoprotein receptor–related protein-4 (LRP4). 7 To date, the doi: 10.1111/nyas.13555 1 Ann. N.Y. Acad. Sci. xxxx (2018) 1–7 C  2018 New York Academy of Sciences.