Mitigation of Lung / Kidney Damage

PROJECT 2 SUMMARY Project 2 of Mitigator Efficacies after Realistic IND Exposures (MERIE) will focus on the unmet need for medical countermeasures (MCM) for the treatment of radiation damage to the lung and kidney. The Medical College of Wisconsin (MCW) team has expertise and established methodologies for the evaluation of delayed effects of acute radiation exposure (DEARE) to the lung and kidney. In keeping with the overall MERIE P01 project objective, Project 2 at MCW will leverage this organ-specific expertise to contribute to the development of a multi-agent approach to mitigate acute and delayed radiation syndromes following exposures anticipated from the detonation of an improvised nuclear device (IND). The biological effects of IND radiation which is heterogeneous in both the type of radiation (mixture of photons/MeV range neutrons) and dose rate (ultra-high dose rate bursts) are likely to differ from X-ray irradiation. Project 2 will increase the understanding of how IND-neutrons and ultra-high dose rate exposures impact the progression of DEARE and biomarker response compared to laboratory X-ray exposures. Three specific aims are proposed: (1) Validate the efficacy of lead candidate MCM lisinopril for mitigation of lung and kidney DEARE following realistic IND exposures; (2) Evaluate the feasibility of a polypharmacy approach to mitigate multi-organ dysfunction following realistic IND exposures, and (3) Identify exposed subjects at risk for progression to lethal lung injury based on an established plasma biomarker panel. Broadly, this work will support the translational goal of developing a comprehensive strategy for diagnosis and treatment of radiation injuries.