Therapeutic strategies targeting complement in myasthenia gravis patients

Abstract

Myasthenia gravis (MG) is an acquired autoimmune disorder characterized by impaired neuromuscular junction transmission, leading to fluctuating muscle weakness. With the progressive identification of MG-related antibodies, such as acetylcholine receptor (AChR) antibodies and muscle-specific kinase (MuSK) antibodies, coupled with advancements in antibody detection technology, the use of these diagnostic markers has become widely accessible in clinical practice. This has facilitated the detection of key biomarkers and enabled the study of targeted therapeutic interventions aimed at addressing the underlying production of MG pathogenic antibodies and their various stages of pathogenicity. Among the emerging therapeutic strategies, complement-targeting drugs have garnered significant attention from medical researchers because of their ability to reduce complement activation and inhibit autoimmune-mediated tissue damage. Inhibition of the terminal complement cascade has demonstrated efficacy in reducing disease severity and improving clinical outcomes, particularly in refractory cases of MG. This review summarizes the underlying mechanisms of complement activation in MG, evaluates the current therapeutic landscape, including both approved and investigational complement inhibitors and discusses the safety considerations of their application.

Keywords: Complement inhibitors; Complement system; Myasthenia gravis; Targeted therapy.

Fig. 1

Complement cascade reaction and MAC formation. MBL: mannose-binding lectin; MASP: MBL-associated serine protease; MAC: membrane attack complex