Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune En-cephalomyelitis.

Remlinger J, Madarasz A, Guse K, Hoepner R, Bagnoud M, Meli I, Feil M, Abegg M, Linington C, Shock A, Boroojerdi B, Kiessling P, Smith B, Enzmann V, Chan A, Salmen A

Neurology: Neuroimmunology & Neuroinflammation · 13 Jan 2022 · doi: 10.1212/NXI.0000000000001134

Visual Acuity in EAE

Demyelinating autoimmune diseases usually impact the optic nerve and thus visual abilities. Optomotor reflex measurements can therefore be used to non-invasively monitor disease progression and treatment efficacy. Remlinger et al studied MOGAD, a rare autoimmune demyelinating CNS disorder, in a murine model of experimental autoimmune encephalomyelitis (EAE). They assessed the effects of treating those mice with monoclonal antibodies against the neonatal Fc receptor and found that this treatment reduced the severity of the disease. Measurements of visual acuity with Striatech’s OptoDrum correlated well with other disease markers.


Background and Objectives Myelin oligodendrocyte glycoprotein antibody–associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS disorder, distinct from multiple sclerosis and neuromyelitis optica spectrum disor-der. Characterized by pathogenic immunoglobulin G (IgG) antibodies against MOG, a potential treatment strategy for MOGAD is to reduce circulating IgG levels, e.g., by interference with the IgG recycling pathway mediated by the neonatal Fc receptor (FcRn). Although the optic nerve is often detrimentally involved in MOGAD, the effect of FcRn blockade on the visual pathway has not been assessed. Our objective was to investigate effects of a monoclonal an-ti-FcRn antibody in murine MOG-IgG–associated experimental autoimmune encephalomyelitis (EAE). Methods We induced active MOG35-55 EAE in C57Bl/6 mice followed by the application of a monoclonal MOG-IgG (8-18C5) 10 days postimmunization (dpi). Animals were treated with either a specific monoclonal antibody against FcRn (α-FcRn, 4470) or an isotype-matched control IgG on 7, 10, and 13 dpi. Neurologic disability was scored daily on a 10-point scale. Visual acuity was assessed by optomotor reflex. Histopathologic hallmarks of disease were as-sessed in the spinal cord, optic nerve, and retina. Immune cell infiltration was visualized by immunohistochemistry, demyelination by Luxol fast blue staining and complement deposition and number of retinal ganglion cells by im-munofluorescence. Results In MOG-IgG–augmented MOG35-55 EAE, anti-FcRn treatment significantly attenuated neurologic disability over the course of disease (mean area under the curve and 95% confidence intervals (CIs): α-FcRn [n = 27], 46.02 [37.89–54.15]; isotype IgG [n = 24], 66.75 [59.54–73.96], 3 independent experiments), correlating with reduced amounts of demyelination and macrophage infiltration into the spinal cord. T- and B-cell infiltration and comple-ment deposition remained unchanged. Compared with isotype, anti-FcRn treatment prevented reduction of visual acuity over the course of disease (median cycles/degree and interquartile range: α-FcRn [n = 16], 0.50 [0.48–0.55] to 0.50 [0.48–0.58]; isotype IgG [n = 17], 0.50 [0.49–0.54] to 0.45 [0.39–0.51]). Discussion We show preserved optomotor response and ameliorated course of disease after anti-FcRn treatment in an experimental model using a monoclonal MOG-IgG to mimic MOGAD. Selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.