Generalized myasthenia gravis (gMG) is a rare autoimmune disorder characterized 
by skeletal muscle weakness caused by disrupted neurotransmission at the 
neuromuscular junction (NMJ). Approximately 74-88% of patients with gMG have 
acetylcholine receptor (AChR) autoantibodies. Complement plays an important role 
in innate and antibody-mediated immunity, and activation and amplification of 
complement results in the formation of membrane attack complexes (MACs), 
lipophilic proteins that damage cell membranes. The role of complement in gMG 
has been demonstrated in animal models and patients. Studies in animals lacking 
specific complement proteins have confirmed that MAC formation is required to 
induce experimental autoimmune MG (EAMG) and NMJ damage. Complement inhibition 
in EAMG models can prevent disease induction and reverse its progression. 
Patients with anti-AChR+ MG have autoantibodies and MACs present at NMJs. 
Damaged NMJs are associated with more severe disease, fewer AChRs, and MACs in 
synaptic debris. Current MG therapies do not target complement directly. 
Eculizumab is a humanized monoclonal antibody that inhibits cleavage of 
complement protein C5, preventing MAC formation. Eculizumab treatment improved 
symptoms compared with placebo in a phase II study in patients with refractory 
gMG. Direct complement inhibition could preserve NMJ physiology and muscle 
function in patients with anti-AChR+ gMG.