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StriatechJournal Club

Anti-FcRn Treatment in Antibody-Associated Experimental Autoimmune Encephalomyelitis

Jana Remlinger, MSc - Department of Neurology, Inselspital, Bern University Hospital and Department for BioMedical Research (DBMR)
Visual Acuity in EAE

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Description

Myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) is a rare, autoimmune demyelinating CNS disorder recently recognized as its own entity, distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. Characterized by pathogenic 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 affected in MOGAD, the effect of FcRn blockade on the visual pathway has not been assessed. Jana Remlinger et al. investigated effects of a monoclonal anti-FcRn antibody in murine MOG-IgG associated experimental autoimmune encephalomyelitis (EAE).
EAE was induced by active MOG35-55 immunization in C57Bl/6 mice and was followed by the application of a monoclonal MOG-IgG (8-18C5) 10 days post immunization (dpi). The mice were treated with a specific monoclonal antibody against FcRn (α-FcRn, 4470, UCB Pharma) on dpi 7, 10 and 13, or with an isotype-matched control IgG. Anti-FcRn antibody, but not the control IgG, significantly attenuated neurological disability (scored on a 10-point scale) over the course of disease. This correlated with histopathological hallmarks of reduced demyelination and macrophage infiltration into the spinal cord. T and B cell infiltration as well as complement deposition remained unchanged. Compared to control IgG, anti-FcRn treatment prevented reduction of visual acuity as assessed by optomotor reflex over the course of disease.
In conclusion, visual function was preserved and the disease course ameliorated after anti-FcRn treatment. Those findings in an experimental model using a monoclonal MOG-IgG to mimic MOGAD suggest that selectively targeting FcRn might represent a promising therapeutic approach in MOGAD.

Key Topics

  • Importance of the visual system in myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and MOG-IgG augmented experimental autoimmune encephalomyelitis (EAE)
  • Mechanism and treatment effects of a specific monoclonal antibody against FcRn in MOG-IgG augmented EAE

Learning Objectives

  • Background on myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and MOG-IgG augmented experimental autoimmune encephalomyelitis.
  • Important aspects of IgG metabolism in the circulation
  • Relevance of targeting the neonatal Fc-receptor (FcRn) when treating antibody-mediated diseases.
  • Concept of visual acuity measurements in such diseases.

Background Reading

Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune Encephalomyelitis. 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.
Neurol Neuroimmunol Neuroinflamm. 2022 Jan 13;9(2):e1134.
doi: 10.1212/NXI.0000000000001134.

Recent Review:

Myelin-oligodendrocyte glycoprotein antibody-associated disease. Marignier R, Hacohen Y, Cobo-Calvo A, et al.
Lancet Neurol. 2021;20(9):762-772.
doi:10.1016/s1474-4422(21)00218-0.

Further information on MOGAD
The following links look at MOGAD from the perspective of patient advocacy groups.

About the speaker

Jana Remlinger, MSc

Jana Remlinger, MSc

PhD Student
Department of Neurology, Inselspital, Bern University Hospital and Department for BioMedical Research (DBMR)

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Jana Remlinger completed her studies in Biomedical Sciences at the Universities of Fribourg and Bern. With both bachelor and master thesis in the field of neurology, she studied motor function in the context of spinal cord injury and neuroinflammation associated with stroke and neuroimmunological diseases. Currently, she is pursuing her PhD project in the neuroimmunological laboratory of Prof. Andrew Chan under the supervision of PD Dr. Anke Salmen (Neuroimmunology) and Prof. Volker Enzmann (Ophthalmology) at the Inselspital Bern. Here, she focuses on antibody-mediated demyelinating disorders of the central nervous system with a special interest in the involvement of the visual pathway.

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Journal Club: Anti-FcRn Treatment in Antibody-Associated Experimental Autoimmune Encephalomyelitis
Mar 22nd, 2022

    Striatech Journal Club - University of Bern

    I already use optomotor measurementsI want to do optomotor measurements in the future

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