Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury

Yicheng Zhu, Naohiro Uezono, Tetsuro Yasui, Masahide Nakajo, Tatsuya Nagai, Dengli Wang, Masahiro Nishibori, Kinichi Nakashima

Research output: Contribution to journalArticlepeer-review

Abstract

Spinal cord injury (SCI) causes motor and sensory deficits and is currently considered an incurable disease. We have previously reported that administration of anti-High Mobility Group Box-1 monoclonal antibody (anti-HMGB1 mAb) preserved lesion area and improved locomotion recovery in mouse model of SCI. In order to further enhance the recovery, we here examined combinatorial treatment of anti-HMGB1 mAb and epothilone B (Epo B), which has been reported to promote axon regeneration. This combinatorial treatment significantly increased hindlimb movement compared with anti-HMGB1 mAb alone, although Epo B alone failed to increase functional recovery. These results are in agreement with that anti-HMGB1 mAb alone was able to decrease the lesion area spreading and increase the surviving neuron numbers around the lesion, whereas Epo B facilitated axon outgrowth only in combination with anti-HMGB1 mAb, suggesting that anti-HMGB1 mAb-dependent tissue preservation is necessary for Epo B to exhibit its therapeutic effect. Taken together, the combinatorial treatment can be considered as a novel and clinically applicable strategy for SCI.

Original languageEnglish
JournalNeuroscience Research
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Axon regeneration
  • Contusion injury
  • Epothilone B
  • Functional recovery
  • High Mobility Group Box-1
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)

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