A review article published on June 20th in the journal Neuroimmunology and Neuroinflammation led by Jun Guo of Tangdu Hospital at The Fourth Military Medical University in Shaanxi, China discusses current and emerging therapeutics for the treatment of neuromyelitis optics (NMO).

Neuromyelitis optics (NMO) is a relapsing-remitting inflammatory demyelinating disease of the CNS that is characterized by recurrent optic neuritis. This inflammation of the optic nerve, a bundle of nerve fibers that transmits visual information from your eyes to the brain can cause pain and temporary vision loss. Optic neuritis is highly associated with multiple sclerosis (MS), a disease in which your autoimmune system attacks the fatty substance that surrounds the nerve fibers in your brain and spinal cord and is essential for the proper functioning of the CNS. However, optic neuritis associated with NMO tends to be more severe than that associated with multiple sclerosis.

Previous studies highlighted by the authors of this review support that as an autoimmune disease, high-levels of the autoantibody targeted to aquaporin 4 (AQP4) in NMO has led to advances in our understanding of NMO. AQP4 is membrane protein expressed by astrocytes (abundant support cell in the brain and help regulate neuronal signaling) and controls the flow of water in cells. Following penetration through the blood-brain barrier and binding to AQP4 on astrocytes AQP4-IgG activates an inflammatory pathway that causes astrocyte cell damage, increased inflammation and eventual demyelination. Due to advances in our understanding of NMO the diagnostic criteria have become independent of multiple sclerosis. AQP4-IgG is a sero-biomarker of NMO and therefore allows NMO to be distinguished from other demyelinating disorders and this eventually lead to the coining of the term neuromyelitis optica spectrum disorder (NMOSD).

Current therapies for NMO are divided into two stages: management of the acute attacks and prevention of future relapses. The most typical route of treatment for acute attacks of NMO is the administration of methylprednisolone, a glucocorticoid with potent anti-inflammatory and immunosuppressive effects. To prevent future attacks Dr. Guo and his group support the current recommendations to administer long-term immunosuppressant's immediately following the first NMO attack. For example, azathioprine, mycophenolate mofetil are commonly used immunosuppressant that both suppress the role of T and B cells. Other agents discussed include mitoxantrone and methotrexate that decrease inflammation associated with NMO by inhibiting specific machinery required by inflammatory cells to proliferate. Another agent that has shown to be promising is rituximab. Currently experimental, rituximab is a chimeric mouse/human anti-CD20 monoclonal antibody that specifically depletes the body of CD20-positive B cells and thereby suppresses the autoimmune reaction.

Dr. Guo and his group also discuss other promising therapies that target specific inflammatory pathways, cytokines, restoring blood-brain barrier integrity, migration of neutrophils and eosinophils, cells key to causing inflammatory in the brain that can lead to demyelination of neurons. For example, a two agents showing promising results include eculizumab, an antibody that inhibits the cleavage of C5, blocking the complement cascade and tocilizumad is interleukin-6 receptor blocking antibody that has shown to decrease the life-span of plasma cells responsible for releasing AQP4-IgG. These and a few agents specific to the activity of neutrophils (i.e. sivelestat) and eosinophils (i.e. cetirizine) have shown significant promise as alternative's to immunosuppressant's in the treatment of NMO. Dr. Guo and his group ultimate goal is developing NMO therapeutics that are highly selective and with low incidences of side-effects.

Article: Current and emerging therapies for neuromyelitis optica, Cong Zhao, Hong-Zeng Li, Ya-Nan Bai, Zhu-Yi Li, Jun Guo, Neuroimmunology and Neuroinflammation, doi: 10.20517/2347-8659.2016.11, published 20 June 2016.