Medicines for NMOSD and MOGAD
A disease with a known target
In most people with NMOSD, the immune system makes antibodies against aquaporin-4, a water channel on astrocytes. The antibody was identified in 2004 and 2005, and it turned a condition long treated as a variant of MS into a separate disease.
Medicines built around the antibody
Each of the new medicines blocks a different step between the antibody and the damage. Eculizumab blocks complement, the part of the immune system that the antibody sets off to destroy astrocytes. Inebilizumab removes B cells through CD19, which is found on a wider range of B cells than CD20, including some that make antibodies. Satralizumab blocks interleukin-6, a signal that helps antibody-making cells survive. In their trials, all three reduced attacks compared with placebo. The evidence is strongest for NMOSD with aquaporin-4 antibodies, and does not establish equal benefit in people without them.
Why some MS medicines can harm
Some medicines that help in MS can make NMOSD worse. In one series, people with NMOSD who were treated with interferon beta had more attacks and higher antibody levels. This is one reason telling the two diseases apart before treatment matters.
MOGAD
MOGAD, defined by antibodies against myelin oligodendrocyte glycoprotein, received its own diagnostic criteria in 2023. Trials of medicines for it are under way, and the Trial Bank lists them.
What this teaches about MS
In MS no single target like aquaporin-4 has been found, so its medicines act broadly on immune cells. If such a target were found, the history of NMOSD suggests that far more precise medicines could follow.
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Key terms
- Myelin
- The fatty sheath wrapped around many nerve fibres in the brain and spinal cord. It lets signals jump quickly along the fibre. MS damages it.
- Oligodendrocyte
- The cell in the brain and spinal cord that makes myelin. One oligodendrocyte can wrap many axons.
- B cell
- A white blood cell that can present targets to T cells, release inflammatory signals and mature into antibody-making cells. Some B-cell-targeting medicines are highly effective MS treatments.
- Astrocyte
- A star-shaped support cell of the brain and spinal cord. In AQP4-positive NMOSD, antibodies target a protein on astrocytes.
- Relapse (attack)
- New or worsening symptoms lasting at least 24 hours, without fever or infection to explain them.
- Placebo
- A dummy treatment that looks like the real one, used so that trial results reflect the medicine itself.
References
- 1. Lennon et al. · A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet (2004)
- 2. Lennon et al. · IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. Journal of Experimental Medicine (2005)
- 3. Pittock et al. · Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder (PREVENT). NEJM (2019)
- 4. Cree et al. · Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum). Lancet (2019)
- 5. Yamamura et al. · Trial of satralizumab in neuromyelitis optica spectrum disorder (SAkuraSky). NEJM (2019)
- 6. Palace et al. · Interferon beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers. Archives of Neurology (2010)
- 7. Banwell et al. · Diagnosis of MOG antibody-associated disease: International MOGAD Panel proposed criteria (2023)
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MS and neurodegenerative diseases
MS is often discussed alongside Alzheimer's disease, Parkinson's disease and ALS, because all of them damage nerve cells over time. This lesson explains what they share, how they differ, and what each field has learned from the others.
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