# rhMFG-E8 as an Effective Adjuvant Therapy for Hemorrhagic Shock

> **NIH NIH R44** · THERASOURCE, LLC · 2021 · $986,433

## Abstract

PROJECT DESCRIPTION: This SBIR Phase II project proposes to further develop recombinant human
milk fat globule epidermal growth factor-factor 8 (rhMFG-E8) as a novel and effective adjuvant therapy for
hemorrhagic shock, which kills 60,000 Americans every year. Hemorrhagic shock results in cell death, and
dying cells release damage-associated molecular patterns (DAMPs). DAMPs promote inflammation,
compounding organ injury to cause multiorgan failure, which is an important cause of morbidity and
mortality after hemorrhage. MFG-E8 is a secreted glycoprotein that promotes the clearance of dying cells,
thus abrogating the release of DAMPs. In our preliminary studies, we have shown that circulating levels of
MFG-E8 are reduced in hemorrhaged mice, and that their adjuvant treatment with His-tagged rhMFG-E8
decreases inflammation and improves hemorrhagic shock survival. Since His-tagged biologics are not
suitable for the use in human patients, we used a human cell expression system to produce pure tag-free
rhMFG-E8, with superior biological activity. In a rat model of hemorrhagic shock, adjuvant treatment with
tag-free rhMFG-E8 significantly reduced the number of apoptotic cells in the liver and lungs, circulating
levels of proinflammatory cytokines and pulmonary infiltration by activated neutrophils. Tag-free rhMFG-E8
also attenuated renal and hepatic injury and improved hemorrhagic shock survival from 50% to 80%.
Additionally, we determined rhMFG-E8’s distribution and elimination half-lifes and its non-carcinogenicity.
Therefore, we hypothesize that tag-free rhMFG-E8 can be further developed as a new and effective
adjuvant therapy for hemorrhagic shock. To advance the drug development, we will determine tag-free
rhMFG-E8’s dose-dependent beneficial effects on organ injury and hemodynamic parameters, as well as its
therapeutic window to improve survival after hemorrhage in the rat. We will also examine tag-free rhMFG-
E8’s safety profile in the rat and verify its beneficial effects on organ injury, hemodynamic parameters, and
survival in a pig model of hemorrhagic shock. These studies will provide critical dosing, time of
administration, efficacy, and safety information to further develop tag-free rhMFG-E8 as an adjuvant therapy
for hemorrhagic shock. Our future steps will include scaling up production of MFG-E8 and completing
efficacy, ADME, and toxicokinetic preclinical studies. 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 tag-
free rhMFG-E8 as a safe and effective resuscitation adjuvant for patients with hemorrhagic shock.

## Key facts

- **NIH application ID:** 10201721
- **Project number:** 5R44HL129543-05
- **Recipient organization:** THERASOURCE, LLC
- **Principal Investigator:** Max Brenner
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $986,433
- **Award type:** 5
- **Project period:** 2016-01-08 → 2023-01-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201721

## Citation

> US National Institutes of Health, RePORTER application 10201721, rhMFG-E8 as an Effective Adjuvant Therapy for Hemorrhagic Shock (5R44HL129543-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10201721. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*