Nuclear accidents and terrorism present a serious threat for causing mass-casualty scenarios. In radiation events, many people receive non-uniform whole-body or partial-body irradiation. The risk of exposure to ionizing radiation due to terrorist activities could result in acute injury as well as long-term adverse health effects in thousands of people. The lung is one of the more radiosensitive organs and inhaling large quantities of radionuclides produces a spectrum of severe functional and morphological changes, ranging from radiation pneumonitis and pulmonary fibrosis. Although efforts to find suitable radiation countermeasures were initiated more than 50 years ago, no safe and effective radiation countermeasure has been approved by the Food and Drug Administration (FDA). Thus, there is a pressing need for radiation countermeasures. Hepatocyte growth factor (HGF) is a paracrine growth factor produced by cells of mesenchymal origin; Activation of the HGF pathway is pulmonary protective and reparative and HGF therapy mitigates lung injury via its c-Met receptor expressed in epithelial and endothelial cells. HGF also protects against fibrotic remodeling following lung injury. HGF protein or gene therapy, however, is not a viable treatment approach especially in a mass casualty setting. BB3 is our first-in-class, bioavailable small molecule HGF mimetic. It has completed Phase I clinical trials and is currently in Phase II safety and efficacy trials for renal and cardiac indications. Our studies are designed to develop BB3 as an effective mitigator of radiation injury by performing the efficacy studies in radiation-induced pneumonitis and pulmonary fibrosis models. These studies are critical for subsequent SBIR phase II studies with the ultimate objective of developing an effective medical countermeasure to use in the clinic.
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