Despite advances in our understanding of excessive alcohol intake-related tissue injury, high morbidity and mortality due to infections in alcohol abusers remain a prominent challenge. Milk fat globule epidermal growth factor-factor VIII (MFG-E8) is involved in the clearance of apoptotic cells. We previously discovered that acute alcohol exposure and infections down regulate MFG-E8 expression. Administration of recombinant murine MFG-E8 (rmMFG-E8) reduces apoptosis, decreases inflammatory responses, and attenuates organ damage in a rat model of acute alcohol exposure and subsequent polymicrobial infections. However, one obstacle that hampered development of MFG-E8 as a therapeutic agent for alcoholic patients with infections is the potential immunogenicity of animal proteins in humans. To overcome this, we successfully expressed and purified recombinant human MFG-E8 (rhMFG-E8), and our data indicated that rhMFG-E8 is as effective as animal MFG-E8. In our SBIR Phase I Contract, we scaled up the production of recombinant human MFG-EB (rhMFG-EB) and confirmed the beneficial effect of rhMFG-EB in a rodent model of acute alcohol exposure and sepsis. The goal of this SBIR Phase II Contract is targeted towards completing the preclinical development of rhMFG-EB as a novel therapeutic agent in reducing mortality after alcohol/sepsis.
