Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb
Abstract 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 barr...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56353-4 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Xinyue Wang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-0a8026acd5cc49d8a08ca2fbf7eedef4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0a8026acd5cc49d8a08ca2fbf7eedef42025-01-26T12:41:20ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-56353-4Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAbXinyue Wang0Ning Li1Lu Han2Ou Qiao3Xin Chen4Pengtao Wang5Lancao Zhang6Yingjie Hou7Fengjiao Bao8Herui Hao9Sania Saeed10Li Zhang11Zizheng Li12Xiaohong Duan13Shuquan Rao14Zichuan Liu15Yanhua Gong16School of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversityState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeSchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversityDepartment of Severe Illnese Medicine, Tianjin First Center HospitalSchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversityState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeSchool of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin UniversitySchool of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56353-4 |
| spellingShingle | 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 Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb Nature Communications |
| title | Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb |
| title_full | Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb |
| title_fullStr | Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb |
| title_full_unstemmed | Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb |
| title_short | Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb |
| title_sort | rescue rm cs aki by blocking strategy with one dose anti myoglobin rabmab |
| url | https://doi.org/10.1038/s41467-025-56353-4 |
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