Vascular endothelial growth factor: A potential target of therapy in neuromyelitis optica?

Abstract

An open study was conducted to evaluate the safety of bevacizumab, antivascular endothelial growth factor antibody, in patients with neuromyelitis optica developing signs of relapse.Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system, which is associated with elevation of pathogenic autoantibodies against the aquaporin 4 (AQP4) water channel. Anti-AQP4 antibodies are assumed to bind to AQP4 protein abundantly expressed in the astrocyte endfoot processes, and the antibody binding leads to complement-dependent damage to astrocytes and disruption of the blood-brain barrier. Currently, there are no approved drugs for NMO, although corticosteroids and immunosuppressive drugs are commonly used in practice with preventive and therapeutic purposes. Approved drugs for multiple sclerosis, including interferon-b, fingolimod and natalizumab, are not recommended for patients with NMO.Analysis of blood and cerebrospinal fluid samples from patients with NMO showed an elevation of inflammatory cytokines and chemokines, including interleukin-6, as well as increased numbers of plasmablasts, which are capable of producing anti-AQP4 antibodies. 1 The potential benefit of blocking the interleukin-6 receptor signaling in NMO has recently been shown in open-labeled trials, implying that ideas for therapy proposed by academia can be very useful in developing new drugs for rare diseases, such as NMO. 2,3 Although not appropriately recognized, an acute attack of NMO can cause complete blindness, serious limb paralysis or neurogenic pain. In contrast, a single symptomatic attack seldom causes such a devastating outcome in MS. In this regard, development of drugs for NMO should aim for complete prevention of relapses or efficacious suppression of acute inflammation during relapse.In the paper published in this issue of Clinical and Experimental Neuroimmunology, Mealy et al. 4 have evaluated the safety of bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, in patients with NMO during relapse. Vascular endothelial growth factor might play a key role in the disruption of the bloodbrain barrier in the inflammatory processes. In this pilot open-labeled study, 10 patients with NMO or NMO spectrum disorder with elevated levels of anti-AQP4 antibodies were enrolled. These patients presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation. Anti-myelin oligodendrocyte glycoprotein antibodies were not measured. In addition to standard intravenous methylprednisolone pulse therapy, bevacizumab was infused on the first day of treatment. As described in the study, bevacizumab add-on therapy was safe in that no adverse event related to the drug was reported by any patient. Bevacizumab might be beneficial in reducing the clinical and pathological signs of NMO relapses, as the patients enrolled in the study did not require plasma exchange as means for escalation ther-