FcRn inhibitors: A new era in neurotherapeutics

The neonatal Fc receptor (FcRn) is a heterodimeric protein that binds albumin and immunoglobulin G (IgG) to mediate pH-dependent recycling, prevent degradation, and maintain their serum concentrations. The ability to bind IgG means FcRn plays both beneficial and potentially detrimental roles in host immunity. Beneficially, FcRn maintains first-line defenses against invading pathogens by preventing degradation of IgG in mucosal secretions, and is linked with increased tumor protection via IgG immune complex-mediated activation of CD8+ cytotoxic T cells and induction of cytotoxic cytokine secretion. FcRn also maintains serum concentrations of circulating pathogenic IgG autoantibodies associated with neurologic and other autoimmune disorders, including myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic inflammatory myopathies. Traditional immune-based therapies for autoimmune disorders, such as steroidal and nonsteroidal immunosuppressants, intravenous and subcutaneous immunoglobulin therapies, and B cell- and complement-targeting therapies, can be associated with significant side-effects and lack of efficacy in some patients. There is a clear need for alternative strategies to treat antibody-mediated autoimmune diseases. The critical role of FcRn in the pathogenesis of autoimmune disorders makes it an ideal target for novel treatments. Here, we discuss the FcRn receptor, current treatments, and recent clinical developments of FcRn-targeting treatments for autoimmune neurologic disorders.