Myasthenia gravis: Molecular mechanisms and promising therapeutic strategies

Zilucoplan: A Newly Approved Macrocyclic Peptide for Treatment of Anti-Acetylcholine Receptor Positive Myasthenia Gravis

“…AChR MG autoantibodies belong to subtypes that mediate tissue damage at the NMJ, while MuSK MG autoantibodies belong to subtypes that, by interfering with proteinprotein interactions at the NMJ, cause direct disruption of AChR signaling [107,108]. When diagnosing the disease, it is extremely important to identify the subtype of the disease, since each subtype has different immunopathologies and the treatments required will therefore be different [91].…”

“…This attack triggers the activation of the antibody-dependent complement system which leads to the formation of MAC. The accumulation of MAC in the post-synaptic membrane of neuromuscular junctions is responsible for their destruction, which leads to muscle weakness (Figure 4A) [108].…”

“…This attack triggers the activation of the antibody-dependent complement system which leads to the formation of MAC. The accumulation of MAC in the post-synaptic membrane of neuromuscular junctions is responsible for their destruction, which leads to muscle weakness (Figure 4A) [108]. Initially, scarce information was available about this disease or its physiological causes and, as a result, the prognosis for patients was very serious and the mortality rate was high.…”

“…Currently, therapeutic strategies for myasthenia gravis disease are divided into two main groups [108]. One group includes traditional therapies such as the use of nonimmunosuppressants such as pyridostigmine, which is an acetylcholinesterase (AChE) inhibitor that increases the amount of ACh in the synapses [115].…”

“…One group includes traditional therapies such as the use of nonimmunosuppressants such as pyridostigmine, which is an acetylcholinesterase (AChE) inhibitor that increases the amount of ACh in the synapses [115]. Among the traditional therapies there are also immunosuppressants such as corticosteroids, calcineurin inhibitors (cyclosporine A, tacrolimus), antimetabolites (cyclophosphamide, mycophenolate mofetil and methotrexate), and intravenous immunoglobulin (IVIG) therapy, with a diverse range of mechanisms of action [108,116]. Plasma exchange (PLEX) is another therapeutic approach, consisting of the direct removal of autoantibodies and complement components involved in the pathogenesis of the disease, in addition with the decrease of pro-inflammatory cytokines levels [117][118][119].…”