Lung transplantation is the only effective treatment modality for patients with end-stage lung disease. Ischemia-reperfusion injury, associated with the retrieval, storage and transplantation of the lung is a major immune-independent factor adversely affecting early graft function, graft viability and recipient morbidity and mortality. Marginal donor lungs, are even more susceptible to ischemia-reperfusion injury, and often fail transplantation. Scatter factor/hepatocyte growth factor has significant protective activity in the setting of pulmonary ischemia-reperfusion injury and additionally, favors pulmonary epithelial repair and regeneration. However its clinical use is limited by the logistical difficulties associated with its administration. During our Phase I program, we have identified Refanalin, an organic small molecule scatter factor/hepatocyte growth factor mimetic that improves lung function secondary to ischemia-reperfusion injury, attenuates pulmonary epithelial death and promotes epithelial regeneration. In a preclinical model of lung cold preservation and transplantation, Refanalin treatment reduced roentgenographic alveolar infiltration, improved pulmonary function and preserved pulmonary microarchitecture. The present Phase II makes an in-depth evaluation of Refanalin efficacy in clinically relevant models of lung transplantation. By attenuating allograft dysfunction and preventing allograft failure, Refanalin can reduce recipient morbidity and mortality. By attenuating ischemia- reperfusion injury in the marginal lung, Refanalin can salvage an otherwise discarded organ, and increase the donor pool.

Public Health Relevance

A small molecule cytoprotective that can be added to the lung preservation solution and administered to graft recipient has significant clinical potential in lung and other solid organ transplantation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44HL080806-03
Application #
7688003
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Reynolds, Herbert Y
Project Start
2005-03-01
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2012-07-31
Support Year
3
Fiscal Year
2009
Total Cost
Indirect Cost
Name
Angion Biomedica Corporation
Department
Type
DUNS #
053129065
City
Uniondale
State
NY
Country
United States
Zip Code
11553