Investigation of pathology and development of therapeutics of NMO using NMO animal models

Abstract

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the CNS. With the discovery of specific serum marker of anti–aquaporin 4 (AQP4) antibody, NMO is now considered to be a distinct disease spectrum from multiple sclerosis (MS). Pathological studies showed that in NMO lesions MBP–stained myelinated fibers were relatively preserved though the AQP4 and GFAP staining are severely lost. The pathogenicity of AQP4–antibody in the pathogenesis of NMO was demonstrated in animal models where patient–derived immunoglobulins were passively transferred. These in vivo studies have shown that AQP4–antibody are capable of inducing astrocyte injury in a complement–dependent manner. Accumulating evidence obtained from further researches utilizing animal models has clarified the involvement of additional type of cells such as T cells, neutrophils, eosinophils, monocytes and microglia in the disease mechanism of NMO. The essential roles of IL–1β and IL–6 have also been demonstrated in several literatures. Based upon these observations obtained by in vivo studies, several novel drugs such as Eculizumab, Inebilizumab, and Satralizumab have been currently proven to be highly effective for the prevention of NMO relapses. Here we discuss the potential role of animal models for the development of future therapeutic targets of NMO.