ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody
Hongen Li,
Mo Yang,
Honglu Song,
Mingming Sun,
Huanfen Zhou,
Junxia Fu,
Di Zhou,
Wenhao Bai,
Biyue Chen,
Mengying Lai,
Hao Kang,
Shihui Wei
Affiliations
Hongen Li
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Mo Yang
Department of Neuro-Ophthalmology, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
Honglu Song
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Mingming Sun
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Huanfen Zhou
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Junxia Fu
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Di Zhou
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Wenhao Bai
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Biyue Chen
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Mengying Lai
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Hao Kang
Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Shihui Wei
Department of Ophthalmology, The Chinese People’s Liberation Army General Hospital & The Chinese People’s Liberation Army Medical School, Beijing 100853, China
Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.
