Monoclonal humanized monovalent antibody blocking therapy for anti-NMDA receptor encephalitis
- Nat Commun. 2025 Jun 17;16(1):5292. doi: 10.1038/s41467-025-60628-1.
- 1. Arialys Therapeutics, Inc., La Jolla, CA, USA.
- 2. Astellas Pharma Inc., Tsukuba, Ibaraki, Japan.
- 3. Center for Neuroscience, University of California, Davis, CA, USA.
- 4. Department of Neurology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
- 5. Vanadro, LLC, Waukee, IA, USA.
- 6. Arialys Therapeutics, Inc., La Jolla, CA, USA. [email protected].
- 7. Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. [email protected].
- # Contributed equally.
Anti-NMDA receptor (NMDAR) encephalitis is a devastating disease with severe psychiatric and neurological symptoms believed to be caused by pathogenic autoantibodies that bind to the N-terminal domain (NTD) of the NMDAR GluN1 subunit (GluN1-NTD) crosslinking adjacent NMDARs and driving their internalization. Here we describe ART5803, a humanized monovalent antibody, as a potential therapy for anti-NMDAR encephalitis. ART5803 binds with a high affinity (KD = 0.69 nM) to GluN1-NTD without affecting NMDAR activity or inducing internalization. ART5803 blocks NMDAR internalization induced by patients' pathogenic autoantibodies, and restores NMDAR function. A marmoset animal model was developed using sustained intracerebroventricular (ICV) administration of a human pathogenic autoantibody to evoke behavioral and motor abnormalities. ART5803 ICV infusion or peripheral injections rapidly reversed these abnormalities. These data, together with the pharmacokinetic profile in cynomolgus monkeys, indicate a therapeutic potential for intravenous (IV)-administered ART5803 as a fast-acting and efficacious option for anti-NMDAR encephalitis.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: iGluRResearch Areas: Inflammation/Immunology