Development and Validation of a Novel Immunotherapy for Traumatic Hemorrhage
Abstract
Despite recent advances in hemorrhage control, traumatic hemorrhage (TH) remains a leading cause of mortality among military and civilian trauma patients. Hemorrhage after trauma is the primary cause of death on the battlefield accounting for 50 percent. Approximately 90 percent of battlefield casualties die in the prehospital environment. In addition, hemorrhage is associated with 85 percent of potentially survivable death in the recent conflicts. Early inflammatory response especially in complement C5 and damage associated molecular patterns represent more generalizable biological principles, which critically regulate systemic inflammatory response syndrome, compensatory anti-inflammatory syndrome, endotheliopathy, and persistent inflammation / immunosuppression and catabolism syndrome, which contribute to multiorgan failure (MOF) and mortality after TH. Therefore, early modulation of these two cascades constitutes a most effective therapeutic principle for the treatment of MOF and the improvement of survival after TH. This project builds on our previous works and well-established capabilities. The program of trauma immunomodulation has successfully proven that anti-C5 or anti-HMGB1 therapy increases survival, improves metabolism and hemodynamics, reduces resuscitation fluid volumes, modulates systemic and local inflammatory responses, and mitigates MOF in a rat TH model. However, the efficacy of inhibition of C5 and/or HMGB1 therapeutic approaches has not been validated in a large animal trauma model at a prolonged field care (PFC) setting. Therefore, this project is to validate the effectiveness of early administration of nomacopan/Nomacopan (C5 inhibitor) and/or CX-01 (HMGB1 inhibitor) therapies aimed to attenuate morbidity and mortality after TH during PFC and prolonged damage control resuscitation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1200777
Entities
People
- Yansong Li
Organizations
- Geneva Foundation