Glatiramer acetate could be a hypothetical therapeutic agent for neuromyelitis optica

Abstract

Neuromyelitis optica (NMO) is characterized by concurrence of optic neuritis and transverse myelitis, which is typically associated with a spinal cord lesion extending three or more vertebral segments. NMO is an inflammatory, demyelinating central nervous system disorder, and although it has a relapsing course in more than 90% of patients, it differs from multiple sclerosis in that it is more severe, usually spares the brain, and is associated with a longitudinally extensive lesion on spinal cord magnetic resonance imaging (MRI). Furthermore, NMO is associated with a highly specific serum marker called anti-aquaporin-4 antibody, which is believed to have a central pathogenetic role in NMO. Treatment with B-cell specific monoclonal antibody (rituximab) and plasma exchanges appears to reduce the severity and frequency of attacks in NMO, and therefore, B-cell autoimmunity as well as a humoral mechanism may be involved in the pathogenesis of NMO. Glatiramer acetate (GA; also known as Copaxone, COP-1) is a synthetic copolymer of a pool of peptides composed of random sequences of four amino acids: glutamine, lysine, alanine, and tyrosine. GA-specific T-helper 1- (Th1) and 2-type (Th2) cells produce brain-derived neurotrophic factor (BDNF), which may affect neuronal survival and myelin repair. GA treatment also leads to sustained augmentation of BDNF, neurotrophin (NT)-3, and NT-4 expression in various brain regions as demonstrated by histological analysis of immunostained brain sections and BDNF elevation after GA treatment on both protein and mRNA levels. GA-Th2 activation may also have a neuroprotective role in the course of NMO. Furthermore, B cells from GA-treated mice suppress experimental autoimmune encephalomyelitis. The pathogenesis of NMO is largely unknown. However, there is some evidence that B-cell autoimmunity, activation of eosinophils, and B-cell activating factor play important roles, based on neurotrophic factors, neuroprotection, anti-inflammation, and B-cell modulation, GA is thus a hypothetic potential treatment agent for NMO.