THERASOURCE, LLC — Department of Health and Human Services SBIR Phase I: NHLBI

Description

DESCRIPTION provided by applicant The primary objective of this project is to further demonstrate the feasibility of developing recombinant human milk fat globule epidermal growth factor factor rhMFG E as a novel and effective adjuvant therapy for the resuscitation of patients with hemorrhagic shock Hemorrhagic shock is a major cause of mortality worldwide In the United States traumatic injury is the main cause of death in individuals younger than years of age and hemorrhagic shock accounts for one third of trauma related deaths Even when treated with the standard of care and in a hospital setting of patients with hemorrhagic shock die within hours Therefore there is an unmet and critical need for a novel and effective adjuvant therapy capable of improving the success rate of the existing volume and vasoactive agents for hemorrhage resuscitation MFG E is a protein that promotes the clearance of apoptotic dying cells and inhibits the production of pro inflammatory cytokines In preliminary studies we treated hemorrhaged animals with rhMFG E and observed significant decreases in circulating pro inflammatory cytokines neutrophil infiltration to the lungs and apoptosis Treatment with rhMFG E also nearly doubled the survival rate from to Therefore we hypothesize that rhMFG E can be further developed as a new and effective adjuvant therapy for hemorrhagic shock To advance the drug development we will produce a new non His tagged rhMFG E and analyze its biological activity homogeneity and folding status We will then determine the dose dependent effects of rhMFG E on reducing organ injury hemodynamic instability pro inflammatory cytokines and histological damage caused by hemorrhagic shock Its therapeutic window to improve survival after hemorrhagic shock will be investigated Finally we will determine its safety pharmacology and pharmacokinetic profile in healthy and hemorrhaged animals Our future steps SBIR Phase II and beyond will include completing preclinical studies such as ADME studies and efficacy studies in a non rodent species as well as comparing with the standard of care We will then file an investigative new drug IND application with the FDA to initiate clinical trials Our ultimate goal is to obtain commercial utilization of rhMFG E as a safe and effective adjuvant drug for the resuscitation of patients with hemorrhagic shock PUBLIC HEALTH RELEVANCE Severe bleeding is a major cause of death worldwide In the United States trauma is the single largest cause of death in people younger than years of age Severe bleeding causes a third of trauma related deaths mostly within the first few hours after trauma Therefore a better treatment for severe bleeding is badly needed We have shown that a protein called rhMFG E strongly protected animals with severe bleeding and improved their survival from to Therefore we propose to further develop rhMFG E as a new and powerful way to treat severe bleeding