FcRN receptor antagonists in the management of myasthenia gravis

Abstract

Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies specifically directed against proteins located within the postsynaptic membrane of the neuromuscular junction. These pathogenic autoantibodies can be reduced by therapies such as plasma exchange, IVIG infusions and other immunosuppressive agents. However, there are significant side effects associated with most of these therapies. Since there is a better understanding of the molecular structure and the biological properties of the neonatal Fc receptors (FcRn), it possesses an attractive profile in treating myasthenia gravis. FcRn receptors prevent the catabolism of IgG by impeding their lysosomal degradation and facilitating their extracellular release at physiological pH, consequently extending the IgG half-life. Thus, the catabolism of IgG can be enhanced by blocking the FcRn, leading to outcomes similar to those achieved through plasma exchange with no significant safety concerns. The available studies suggest that FcRn holds promise as a versatile therapeutic intervention, capable of delivering beneficial outcomes in patients with distinct characteristics and varying degrees of MG severity. Efgartigimod is already approved for the treatment of generalized MG, rozanolixizumab is under review by health authorities, and phase 3 trials of nipocalimab and batoclimab are underway. Here, we will review the available data on FcRn therapeutic agents in the management of MG.

Keywords: Fc receptor inhibitors; clinical trials; immunoglobulins (IgG); myasthenia gravis (MG); neonatal Fc receptor (FcRn).

Figure 1

FcRn mediated recycling. (A) The binding of IgG and albumin to the FcRn receptors prolongs their half-lives due to the prevention of lysosomal degradation. (B) Binding of the FcRn therapeutic agent, thus preventing the recycling of IgG due to increased lysosomal degradation.