Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy

Junli Zhao, Yi Wang, Cenglin Xu, Keyue Liu, Ying Wang, Liying Chen, Xiaohua Wu, Feng Gao, Yi Guo, Junming Zhu, Shuang Wang, Masahiro Nishibori, Zhong Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients. The mAb showed an anti-seizure effect with a long-term manner and appeared to be minimal side effects at even very high dose (no disrupted physical EEG rhythm and no impaired basic physical functions, such as body growth rate and thermoregulation). This anti-seizure effect of mAb results from its inhibition of translocated HMGB1 from nuclei following seizures, and the anti-seizure effect was absent in toll-like receptor 4 knockout (TLR4-/- ) mice. Interestingly, the anti-HMGB1 mAb also showed a disease-modifying anti-epileptogenetic effect on epileptogenesis after status epileptics, which is indicated by reducing seizure frequency and improving the impaired cognitive function. These results indicate that the anti-HMGB1 mAb should be viewed as a very promising approach for the development of novel therapies to treat refractory epilepsy.

Original languageEnglish
JournalBrain, Behavior, and Immunity
DOIs
Publication statusAccepted/In press - Oct 23 2016

Fingerprint

Epilepsy
Seizures
Monoclonal Antibodies
Therapeutics
HMGB1 Protein
Electroshock
Pentylenetetrazole
Toll-Like Receptor 4
Body Temperature Regulation
Kainic Acid
Encephalitis
Human Activities
Knockout Mice
Cognition
Electroencephalography
Brain
Growth

Keywords

  • Epilepsy
  • HMGB1
  • Monoclonal antibody

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy. / Zhao, Junli; Wang, Yi; Xu, Cenglin; Liu, Keyue; Wang, Ying; Chen, Liying; Wu, Xiaohua; Gao, Feng; Guo, Yi; Zhu, Junming; Wang, Shuang; Nishibori, Masahiro; Chen, Zhong.

In: Brain, Behavior, and Immunity, 23.10.2016.

Research output: Contribution to journalArticle

Zhao, Junli ; Wang, Yi ; Xu, Cenglin ; Liu, Keyue ; Wang, Ying ; Chen, Liying ; Wu, Xiaohua ; Gao, Feng ; Guo, Yi ; Zhu, Junming ; Wang, Shuang ; Nishibori, Masahiro ; Chen, Zhong. / Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy. In: Brain, Behavior, and Immunity. 2016.
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