As we come to the end of the NMOSD awareness month, in this article, we will look at the journey so far for patients, caregivers, prescribers and scientists interested in NMOSD

The new millennium brought major advances in the treatment of NMOSD. In chronological order, these include:

1. NMOSD is NOT MS (1999–2004)

At the dawn of the millennium, NMOSD (then called Devic’s disease) was widely considered a severe form of Multiple Sclerosis

• Achievement: In 2004, researchers at the Mayo Clinic discovered the AQP4-IgG antibody
• Impact: This proved that NMOSD is an astrocytopathy, whereas MS is primarily a demyelinating disease. This discovery prevented thousands of patients from receiving MS medications that either did not improve or even worsened their condition

2. We have a culprit (for 80% of the cases) (2006)

In 2004, the team led by Dr. Vanda Lennon at the Mayo Clinic identified a water channel protein, Aquaporin-4 (AQP4), as the target of the immune system

• Achievement: The 2006 Wingerchuk Criteria officially incorporated AQP4-IgG testing into the diagnosis
• Impact: This could confirm the disease with over 90% specificity

3. It’s a neurological “spectrum,” not just an “eye” disease (2015)

Physicians realised patients didn’t just have eye and spinal cord issues; they also had brainstem issues (like uncontrollable hiccups/nausea from Area Postrema Syndrome) and “brain fog” 

• Achievement: The International Panel for NMO Diagnosis (IPND) published the revised 2015 criteria, officially naming the disease Neuromyelitis Optica Spectrum Disorder (NMOSD)
• Impact: Patients with “atypical” symptoms were treated early before they suffered a major disabling attack

4. If it’s not AQP4, it may be MOG (2017–2018)

The large “Seronegative” NMOSD was further differentiated into those positive for Myelin Oligodendrocyte Glycoprotein (MOG) antibody

• Achievement: Formalization of MOG-Antibody Disease (MOGAD) as a separate clinical entity
• Impact: This allowed for cleaner clinical trials and more specific treatment plans for both groups, as MOGAD often responds better to steroids and differently to biologics

5. The start of the targeted therapy era (2019–2020)

Even after the clarity on the etiology and pathogenesis, NMOSD was treated with off-label, broad-spectrum immunomodulators, such as rituximab or azathioprine

• Achievement: In a short 18-month window, the FDA approved three targeted biologics:
  1. Eculizumab (Soliris) – PREVENT Trial
  2. Inebilizumab (Uplizna) – N-MOmentum Trial
  3. Satralizumab (Enspryng) – SAkura Trials
• Impact: Relapse reduction rates reached ~90-100% (for the C5 inhibitors) in many cohorts, making most patients “relapse-free”

So with all these achievements, the reader may ask why the pessimism in the title? Unfortunately, NMOSD still remains a life-altering and highly debilitating disease for many. Some of the unmet needs and unknowns are:


1. Not all “seronegatives” are MOGAD – so who are the remaining?

Around 20–30% of NMOSD patients do not have detectable AQP4-IgG antibodies. Of these “seronegative” patients 50% have MOG antibodies (MOGAD), while the remaining are double-seronegative”

2. Relapse prevention is not symptom clearance

Many NMOSD patients suffer from chronic neuropathic pain, fatigue abd brain fog. None of the currently FDA-approved biologics (C5 inhibitors or IL-6 blockers) is indicated to treat these symptoms

3. Stopping does not mean reversal

While relapse prevention has been largely achieved, repair and remyelination are still in the early experimental stages. Even in MS, where a log order higher number of trials have been conducted testing repair strategies, this is an elusive goal

4. Life-long treatment means NMOSD patients are always patients

Current SOCs, while brilliant in relapse prevention, require indefinite treatment. A “one-and-done” treatment by reprogramming T-cells to eliminate the B-cells responsible for AQP4 antibodies is still in the trial stages

5. NMOSD is a million-dollar disease

Even when covered by insurance, the cost of NMOSD treatment is very high. The launch of eculizumab biosimilars in the US and Europe has reduced some costs, but the lifelong treatment makes this one of the few million-dollar diseases (with maintenance treatment costs reaching ~$500K a year)

Sources:

Lennon VA, et al. (2004). “A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.” The Lancet.

Wingerchuk DM, et al. (2006). “Revised diagnostic criteria for neuromyelitis optica.” Neurology.

Wingerchuk DM, et al. (2015). “International consensus diagnostic criteria for neuromyelitis optica spectrum disorder.” Neurology.

Pittock SJ, et al. (2019). “Eculizumab in Aquaporin-4–Positive Neuromyelitis Optica Spectrum Disorder.” New England Journal of Medicine (NEJM).

Cree BAC, et al. (2019). “Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial.” The Lancet.

International Panel for NMO Diagnosis (IPND) 2025/2026 Surveillance Report; DelveInsight NMOSD Market Analysis (March 2026).