A Defined Patho-Mechanism for Acute Radiation Syndrome Death and a Three-Drug Regimen to Prevent It

Death from acute radiation syndrome (ARS) has been a long-standing threat. Given the current heightened risk of a nuclear event, e.g., a conflict bomb, terror bomb, reactor core dispersion, or recurrent exposure to medical radiation, a systemic treatment to reduce or eliminate ARS death would be beneficial. This study utilizes step-wise progression to (i) identify why lethally irradiated mice die from ARS and (ii) identify a multidrug regimen, administered before or after irradiation, that prevents or treats ARS pathologies to significantly suppress or eliminate ARS death. Lethal blood-borne E. coli septic infection was found in 97% of near-death, irradiated mice; this observation was consistent with the numerous breaches observed in GI histology showing a broken and breached GI epithelium and GI muscularis externa. Our study found (i) a new and clear explanation of why irradiated mice die from ARS; (ii) identified two drugs (PrC-210, ciprofloxacin), which, when administered minutes pre-radiation, conferred 100% survival benefit or 56% when administered a day after irradiation; and (iii) a three-drug regimen (PrC-210, ciprofloxacin, GCSF) that conferred 92% survival benefit when administered 1-2 days after radiation. These drug regimens can be "field-deployed" to field staging areas and home medicine chests to enable the simple, widespread use of the regimens in the face of radiation threat.