Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb

作者：Xinyue Wang, Ning Li, Lu Han, Ou Qiao, Xin Chen, Pengtao Wang, Lancao Zhang, Yingjie Hou, Fengjiao Bao, Herui Hao, Sania Saeed, Li Zhang, Zizheng Li, Xiaohong Duan, Shuquan Rao, Zichuan Liu, Yanhua Gong · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-56353-4 · 被引用次数：5 · 研究领域：Muscle and Compartmental Disorders、Poisoning and overdose treatments、Drug-Induced Adverse Reactions

Rhabdomyolysis or Crush syndrome-related AKI (RM/CS-AKI) has high mortality, and there is no effective early on-site treatment method. The critical pathogenic factor of RM/CS-AKI is the excessive free myoglobin (Mb) in blood circulation. Here, based on the concept of creating a “mobile barrier”, we develop an anti-Mb rabbit monoclonal antibody (RabMAb) with high specificity, affinity, stability, and broad species reactivity. A single dose of anti-Mb RabMAb injection is sufficient for emergency rescue in both homologous and heterologous RM/CS-AKI male animal models. The main goal of blocking the passage of free Mb through the glomerular filtration barrier has been achieved by using the anti-Mb RabMAb, which has a long-term stable therapeutic effect within 14 days and promotes phagocytosis of Mb. The optimal administration strategy, pharmacokinetic analysis, toxicity evaluation for anti-Mb RabMAb, and the distribution of its immune complexes in RM/CS-AKI mice are investigated. Thus, we develop effective prevention and control strategies for RM/CS-AKI. Myoglobin (Mb) is the critical pathogenic factor for Rhabdomyolysis or Crush syndrome-related AKI (RM/CS-AKI). Here, the authors show that anti-Mb RabMAb injection blocking the passage of free Mb through the glomerular filtration barrier significantly rescues both homologous and heterologous RM/CS-AKI animal models.