Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Pharmacology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
Neurosci Res. 2021 Nov;172:13-25. doi: 10.1016/j.neures.2021.04.002. Epub 2021 Apr 18.
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.
脊髓损伤（SCI）导致运动和感觉功能缺损，目前被认为是一种不可治愈的疾病。我们之前的研究报告显示，给予抗高迁移率族蛋白 B1 单克隆抗体（anti-HMGB1 mAb）可保留损伤面积并改善 SCI 小鼠模型的运动功能恢复。为了进一步增强恢复效果，我们在此研究了抗 HMGB1 mAb 和埃坡霉素 B（Epo B）的联合治疗，Epo B 已被报道可促进轴突再生。与单独使用抗 HMGB1 mAb 相比，这种联合治疗显著增加了后肢运动，尽管单独使用 Epo B 并不能增加功能恢复。这些结果与以下事实一致：单独使用抗 HMGB1 mAb 能够减少损伤面积的扩散并增加损伤周围存活神经元的数量，而 Epo B 仅在与抗 HMGB1 mAb 联合使用时才促进轴突生长，这表明抗 HMGB1 mAb 依赖性组织保存对于 Epo B 发挥治疗作用是必要的。综上所述，联合治疗可被视为 SCI 的一种新的、具有临床应用潜力的策略。
