Work

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

Year: 2014

Type: review

Abstract: Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerve, and can lead to paralysis and blindness. Currently, several treatment options for NMO exist, but many have been adapted from multiple sclerosis, and no controlled clinical trials specific to NMO have been conducted to date. Here, Marios Papadopoulos and colleagues review the various treatment strategies in NMO, and discuss the drugs that are in development or could be repurposed to treat this condition. Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood–brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19—all initially developed for other indications—are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood–brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date.

Source: Nature Reviews Neurology

DOI: 10.1038/nrneurol.2014.141

Authors: Marios C. Papadopoulos, Jeffrey L. Bennett, Alan S. Verkman

Institutions: St George's, University of London, University of Colorado Anschutz, University of Colorado Denver, University of California, San Francisco

Language: English

Topic: Multiple Sclerosis Research Studies

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Guthy-Jackson Charitable Foundation, National Institutes of Health, National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases