THERASOURCE, LLC — Department of Health and Human Services SBIR Phase I: 400

Description

PROJECT DESCRIPTION The primary objective of this project is to demonstrate the feasibility of developing recombinant human milk fat globule epidermal growth factor factor rhMFG E as a novel and effective therapeutic for patients with acute kidney injury AKI associated with ischemia due to low renal perfusion AKI is a major cause of prolonged hospitalization and increased mortality Ischemic AKI often results from decreased renal blood flow associated with cardiac surgery involving cardiopulmonary bypass especially coronary artery bypass graft and valve replacement Despite being a frequent life shortening and costly complication no FDA approved drugs are currently clinically available to treat ischemic AKI MFG E is a protein that promotes the clearance of inflammation promoting dying cells and decreases the influx of tissue damaging neutrophils to the injured site In the preliminary study we used recombinant mouse MFG E to treat mice with AKI induced by severe renal ischemia reperfusion Treatment with recombinant mouse MFG E significantly attenuated renal dysfunction decreased levels of proinflammatory cytokines and reduced kidney infiltration by neutrophils Therefore we hypothesize that rhMFG E can be developed as a new and effective biologic drug to treat patients with ischemic AKI Indeed administration of His tagged rhMFG E increased the day survival of mice with ischemic AKI from to Since His tagged proteins are not suited for use in humans we have started to produce a druggable human like glycosylated His tag free rhMFG E using a mammalian Chinese hamster ovary CHO cell expression system In this project we will express purify and characterize CHO expressed rhMFG E We will next determine CHO expressed rhMFG E andapos s efficacy to attenuate renal injury and improve survival after ischemic AKI and its pharmacokinetic PK profile in healthy and AKI animals Our future steps SBIR Phase II and beyond include completing preclinical and safety studies establishing ADME and safety studies determining efficacy in a second species and filing an investigational 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 biologic drug to treat patients with ischemic AKI PUBLIC HEALTH RELEVANCE STATEMENT During many common surgical procedures such as coronary artery heart valve replacement and cancer surgery the blood flow to the kidneys may drop resulting in acute kidney injury Acute kidney injury leads to a loss of kidney function longer hospital stays expensive treatments and increased death Yet there is no good treatment for patients with acute kidney injury We have shown that a protein called MFG E strongly protects experimental animals from acute kidney injury and improves their survival Therefore we propose to develop the human form of MFG E as a new and powerful way to treat surgery associated acute kidney injury