Aquaporin 4 and neuromyelitis optica

Abstract

Neuromyelitis optica is an inflammatory demyelinating disorder of the CNS. The discovery of circulating IgG1 antibodies against the astrocyte water channel protein aquaporin 4 (AQP4) and the evidence that AQP4-IgG is involved in the development of neuromyelitis optica revolutionised our understanding of the disease. However, important unanswered questions remain—for example, we do not know the cause of AQP4-IgG-negative disease, how astrocyte damage causes demyelination, the role of T cells, why peripheral AQP4-expressing organs are undamaged, and how circulating AQP4-IgG enters neuromyelitis optica lesions. New drug candidates have emerged, such as aquaporumab (non-pathogenic antibody blocker of AQP4-IgG binding), sivelestat (neutrophil elastase inhibitor), and eculizumab (complement inhibitor). Despite rapid progress, randomised clinical trials to test new drugs will be challenging because of the small number of individuals with the disorder.

Longitudinally extensive transverse myelitis with AQP4 antibodies revealing ovarian teratoma

“…Autoreactive lymphocytes originating in the teratoma could enter the blood stream, cross the blood-brain barrier and cause the neurological disease. Alternatively AQP4 antibodies might be produced peripherally and enter the CNS secondarily (Papadopoulos and Verkman, 2012). In a recent report of a patient with paraneoplastic myelitis, breast cancer and AQP4 antibodies, the tumor was also found to express the AQP4 antigen (Armağan et al, 2012).…”

Neuromyelitis optica in Portugal (NEMIPORT) – A multicentre study

“…NMO is a rare inflammatory demyelinating disease of the central nervous system (CNS) [1], with an estimated prevalence of 0.3-4.4/100.000 [2]. It is more prevalent in females (9:1) [1].…”

Glyphosate pathways to modern diseases VI: Prions, amyloidoses and autoimmune neurological diseases

“…Neuromyelitis optica is a rare severe inflammatory demyelinating disorder of the central nervous system, which is related to multiple sclerosis but distinctly different and manifested mainly by paralysis and optic nerve damage [177,178]. It has been conclusively demonstrated that this condition is caused by an autoimmune reaction to aquaporin-4, which is highly expressed in the astrocyte membrane [177,178].…”

“…It has been conclusively demonstrated that this condition is caused by an autoimmune reaction to aquaporin-4, which is highly expressed in the astrocyte membrane [177,178].…”