Neuromyelitis Optica Spectrum Disorder

Despite first being described 125 years ago, it has remained a common myth that neuromyelitis optica spectrum disorder (NMOSD) is a variant of multiple sclerosis (MS).

Although in both conditions the body's own immune system attacks the optic nerves, brain, and spinal cord resulting in a destruction of the insulating layer of nerve cells (known as the myelin sheath), they have different origins that came to light less than a decade ago. NMOSD can actually be more severe and unpredictable than MS, making early and accurate diagnosis crucial.

Because NMOSD and MS can look very similar, a high rate of misdiagnosis still occurs, leading to people with NMOSD being treated with MS therapies, some of which are ineffective, even causing deterioration in people with NMOSD.

After a long debate, the breakthrough in distinguishing between NMOSD and MS was the discovery of the aquaporin-4 (AQP4) antibody.1 AQP4 proteins play a crucial role in water transportation as well as maintaining balance (called homeostasis) within the central nervous system.2 The AQP4 antibodies target the AQP4 protein causing inflammatory damage to specific cells in the brain called astrocytes.1

Initially, it was thought that neuromyelitis optica (NMO) was limited to inflammation of the optic nerve (optic neuritis) and spinal cord (acute myelitis).1 However, as other brain syndromes also occur in NMO, the term NMO spectrum disorder (NMOSD) was proposed in 2015 to cover a broader clinical spectrum – as a result, measures for diagnosis have been clarified over the past few years.1

Cases of NMO were first published by researcher Eugene Devic – became known as Devic’s disease⁵

First proposed criteria for diagnosing NMO, which included inflammation of the optic nerve (optic neuritis) and spinal cord (acute myelitis)

First report of an autoantibody (an antibody created by an individual that is directed against that person’s own proteins) unique to NMO – the next year the target was identified as the AQP4 antibody

Researchers incorporated positive testing for the AQP4 antibody (known as seropositivity) in the criteria for diagnosing NMO. Both optic neuritis and acute myelitis remained requirements

Researchers introduced the term ‘NMOSD’, to cover a broader spectrum of conditions, including brain syndromes

Publication of The International Consensus Diagnostic Criteria of Neuromyelitis Optica Spectrum Disorders. This proposed two sub-groups of NMOSD patients, and additional criteria for diagnosis

The two sub-groups of NMOSD patients included in the 2015 diagnostic criteria were:

• Those with AQP4 antibodies in their blood (called AQP4 antibody seropositive NMOSD)

• Those without AQP4 antibodies in their blood (called AQP4 antibody seronegative NMOSD)

Despite the considerable success in understanding NMOSD more deeply, researchers and scientists are continuing to work hard to reveal more about this complex condition.

Much of the research focuses on a better understanding of the complicated overlap between NMOSD and other conditions, to ensure the most accurate diagnosis can be made promptly. One example is to understand the nature of people who do not express the AQP4 antibody but who show the same clinical characteristics as NMOSD – those who are 'AQP4 antibody seronegative'.1

Myelin Oligodendrocyte Glycoprotein (MOG) is a protein found on the myelin sheath. A MOG antibody has been detected in some people with AQP4 antibody seronegative NMOSD, but not in those with AQP4 antibody seropositive NMOSD. As a result, it has been proposed that AQP4 antibody seropositive NMOSD and anti-MOG syndromes are separate conditions.3

The 21st Century has heralded a significant advancement of our understanding of NMOSD, developing in-depth knowledge and new treatments.

Recent approvals for new, effective treatment options have been welcomed by those living with NMOSD, which can have a profound impact on people.4 At Roche, we are committed to playing a significant part in this advancement, taking an innovative approach to research and development.

We never stop following the science, ensuring we’re doing now what patients need next, to help preserve what makes people who they are.