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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
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.
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publishDate 2025-01-01
publisher Nature Portfolio
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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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