Treatment of neuromyelitis optica: state-of-the-art and emerging therapies
Marios C Papadopoulos, Jeffrey L Bennett, Alan S Verkman, Marios C Papadopoulos, Jeffrey L Bennett, Alan S Verkman
Abstract
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.
Conflict of interest statement
Competing interests
M.C.P. has received consulting income from ONO Pharmaceutical. J.L.B. has received consulting income from MedImmune and Chugai Pharmaceuticals. He has a patent application on aquaporumab technology and is a member of the board of directors of Apsara Therapeutics. A.S.V. has patent applications on aquaporumab and EndoS technology and is a member of the board of directors of Apsara Therapeutics.
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Source: PubMed