What is Neuromyelitis Optica Spectrum Disorder?
 

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune disorder of the central nervous system characterized primarily by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis. These attacks often lead to severe vision loss, motor, and sensory dysfunction.

According to recent studies, the prevalence of NMOSD is approximately 1.82 per 100,000 individuals. Prevalence is significantly higher in African and Asian populations compared to Caucasian populations, and females are affected much more frequently than males (approximately a 10:1 ratio).
 

Pathogenesis
 

The core pathogenesis of NMOSD is closely linked to the presence of autoantibodies against aquaporin-4 (AQP4).

Peripheral immune dysregulation leads to the differentiation of Th17 cells, which produce inflammatory cytokines such as interleukin-17A (IL-17A) and interferon-gamma (IFN-γ). These cytokines further promote B cell differentiation into plasma cells, generating more AQP4-IgG and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) autoantibodies. These autoantibodies enter the central nervous system (CNS) by crossing the blood-brain barrier (BBB).

AQP4-IgG binds to AQP4 on the surface of astrocytes. This binding activates the complement system, triggering complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), leading to astrocyte damage and subsequent demyelination. Concurrently, MOG-IgG binds to myelin oligodendrocyte glycoprotein (MOG), activating the complement cascade, further promoting inflammatory cell infiltration and neural damage, ultimately resulting in axonal degeneration and neurological dysfunction.
 

(Image: MDPI)

Gene Therapy
 

● CAR-T Cell Therapy: In 2023, the research team led by Professor Wang Wei at Huazhong University of Science and Technology initiated a clinical trial of CAR-T cell therapy for AQP4-IgG-seropositive NMOSD patients. The study indicated that CAR-T cell therapy shows manageable safety and therapeutic potential for patients with relapsed/refractory AQP4-IgG-seropositive NMOSD.

(Image: CAR-T Cell Therapy)

● Gene Editing Technology: Involves genetically modifying immune cells to restore immune tolerance. This approach remains in the research stage but shows potential for modulating immune pathways and restoring antigen-specific immune tolerance.
 

Mouse Models
 

● hAQP4 Mice: Express the human AQP4 protein. This model is widely used to simulate the pathological processes of NMOSD. Passive transfer of AQP4-IgG and human complement successfully induces typical pathological changes in this model, including astrocyte damage, inflammatory response, and demyelination.

● AQP4 KO Mice: Mice lack the AQP4 protein. They are used to study the function of the AQP4 protein in physiological and pathological states and serve as a crucial negative control for antibody pathogenicity studies, confirming the target specificity of AQP4-IgG.
 

MingCeler Biotech Facilitates Gene Therapy
 

Gene therapy offers hope for rare diseases, but its development and validation are inseparable from animal model support. Leveraging its self-developed TurboMice™ technology, MingCeler Biotech has developed multiple rare disease mouse models. The TurboMice™ technology overcomes the challenges of long modeling cycles and low success rates for complex models. It enables editing at virtually any target gene locus and can generate complete homozygous gene-edited mouse models directly from embryonic stem cells in as little as 2 months.

MingCeler Biotech can customize various NMOSD mouse models according to client needs, such as hAQP4 mice and AQP4 KO mice. We welcome inquiries!

 

References:

[1] Jia Linlin, Jiang Yushu, Zhang Mengge, Ma Weifeng, Zhang Tao, Li Wei. Research Progress on the Pathogenesis of Neuromyelitis Optica Spectrum Disorder. Journal of Clinical Medicine in Practice, 2022, 26(7): 132-138. DOI: 10.7619/jcmp.20215000

[2] Huang, T.-L.; Wang, J.-K.; Chang, P.-Y.; Hsu, Y.-R.; Lin, C.-H.; Lin, K.-H.; Tsai, R.-K. Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives. Int. J. Mol. Sci. 2022, 23, 7908. https://doi.org/10.3390/ijms23147908

[3] Pittock, S.J., Zekeridou, A. & Weinshenker, B.G. Hope for patients with neuromyelitis optica spectrum disorders — from mechanisms to trials. Nat Rev Neurol 17, 759–773 (2021). https://doi.org/10.1038/s41582-021-00568-8

[4] Xu L, Xu H, Tang C. Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders: progress of experimental models based on disease pathogenesis. Neural Regen Res. 2025 Feb 1;20(2):354-365. doi: 10.4103/NRR.NRR-D-23-01325. Epub 2024 Jan 31. PMID: 38819039; PMCID: PMC11317952.

[5] Correale J, Carnero Contentti E. Induction of immune tolerance in NMOSD and MOGAD. Ther Adv Neurol Disord. 2025 Aug 1;18:17562864251357393. doi: 10.1177/17562864251357393. PMID: 40761287; PMCID: PMC12319201.

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