Orthotopic liver transplantation is the most effective treatment for patients with end-stage liver disease. Ischemia-reperfusion injury associated with the retrieval, storage and transplantation of livers is a major immune-independent factor adversely affecting early graft function, and limiting long-term graft survival. Marginal donors livers, including steatotic livers, are even more susceptible to ischemia-reperfusion injury, and often fail transplantation. Scatter factor/hepatoyte growth factor is a hepatotrophic factor with significant hepatoprotective activity. However its clinical use is limited by the logistical difficulties associated with its administration. We have identified Refanalin, an organic small molecule scatter factor/hepatocyte growth factor mimetic, with significant cytoprotective activity. In animal models of organ-specific ischemic injury, Refanalin attenuates infarct size and improves function. In in vivo global hepatic ischemia-reperfusion, Refanalin reduces hepatic injury, attenuates hepatocyte apoptosis and necrosis and preserves hepatic ultrastructure. The present Phase II proposal explores the therapeutic potential of Refanalin in clinically relevant models of orthotopic liver transplant. By attenuating allograft dysfunction and preventing allograft failure, Refanalin can reduce recipient morbidity and mortality. By attenuating ischemia-reperfusion injury in the marginal liver, Refanalin can salvage an otherwise discarded organ, and increase the donor pool.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AA014718-03
Application #
6942332
Study Section
Special Emphasis Panel (ZRG1-SSS-8 (10))
Program Officer
Purohit, Vishnu
Project Start
2003-05-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$637,350
Indirect Cost
Name
Angion Biomedica Corporation
Department
Type
DUNS #
053129065
City
Garden City
State
NY
Country
United States
Zip Code
11553