Abstract

Neuromyelitis optica (NMO) is a chronic inflammatory disease of the central nervous system that primarily affects the optic nerves and spinal cord of patients, and in some instances their brainstem, diencephalon or cerebrum as spectrum disorders (NMOSD). Clinical and basic science knowledge of NMO has dramatically increased over the last two decades and it has changed the perception of the disease as being inevitably disabling or fatal. Nonetheless, there is still no cure for NMO and all the disease-modifying therapies (DMTs) are only partially effective. Furthermore, DMTs are not disease- or antigen-specific and alter all immune responses including those protective against infections and cancer and are often associated with significant adverse reactions. In this review, we discuss the pathogenic mechanisms of NMO as they pertain to its DMTs and immune tolerance. We also examine novel research therapeutic strategies focused on induction of antigen-specific immune tolerance by administrating tolerogenic immune-modifying nanoparticles (TIMP). Development and implementation of immune tolerance-based therapies in NMO is likely to be an important step toward improving the treatment outcomes of the disease. The antigen-specificity of these therapies will likely ameliorate the disease safely and effectively, and will also eliminate the clinical challenges associated with chronic immunosuppressive therapies.

Highlights

  • Neuromyelitis optica (NMO) is a rare autoimmune disorder mediated by self-reactive T and B cells, and an antibody against the aquaporin 4 (AQP4) channel protein of astrocytes [1]

  • We examine a novel therapeutic strategy based on tolerogenic immune-modifying nanoparticles (TIMP) and its potential clinical significance [17]

  • Immunotherapy of NMO continues to evolve and to adapt to the new clinical and research advancements related to enhanced understanding of the disease pathogenesis

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Summary

INTRODUCTION

Neuromyelitis optica (NMO) is a rare autoimmune disorder mediated by self-reactive T and B cells, and an antibody against the aquaporin 4 (AQP4) channel protein of astrocytes [1]. The autoimmune reaction in NMO arises in the secondary immune organs as a result of a failure of immune tolerance, pro-inflammatory antigen presentation, and emergence of anti-AQP4 antibody and Th17 cells. DMTs are not antigen-specific or disease-specific, and none of them aim for the eradication of the self-reactive immune cells or result in anti-AQP4 seroreversion Their efficacy is based on establishing a state of chronic immunosuppression, where all immune responses are altered, including those protective against infections and cancer. Interest in the immune tolerance approach for treatment of NMO stems from the fact that the autoimmune response is directed against a well-defined antigen and the anti-AQP4 antibody is simultaneously an effector molecule as well as a biomarker marker of the disease, thereby providing a direct measure of treatment efficacy.

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