Manganese-peptide Countermeasures for Radiation Exposure

The toxicity of ionizing radiationIRin diverse cell types is associated with a high susceptibility of the proteome to oxidative modificationProteome protection as a tactic for IR survival was recently applied to mice using a synthetic Mn peptide antioxidant complexMDPthat specifically prevents protein oxidation and preserves the activity of irradiated enzymesincluding those for cellular DNA repairMDPadapted from the radioresistant bacterium Deinococcus radioduransis nontoxic and protects mice from acute radiation syndromesARSWhen administered preand post irradiationall the mice treated with MDP survivedGyLDMDP diminished ARS and increased serum levels of ILG CSF and GM CSFThe radioprotective efficacy of MDP administered to mice post irradiationhoweverremains untestedNotethere is good reason to think that post exposure treatment alone with MDP will be radioprotectiveMDP protects human Jurkat T cells exposed toGy when administeredhours post irradiationWe propose to determine whether MDP could serve as an IR countermeasure when administered startingorhours after exposure to x ray irradiationThe MDP complex will be tested in a standard mouse model for total body irradiation induced ARScontrolled for age and dietfocusing on tissueand immunological functions among the survivors Potential radiological exposure from terrorist actsnuclear warheadsand power plant accidents have been a continual source of concern to scientistspoliticiansand the general populaceNo drugs have been approved that mitigate lethal exposures and lead to survivalWe propose to assess a manganese decapeptide phosphateMDPcomplex that protects all proteins from ionizing radiation damage under aqueous conditionsThe MDP complex has been shown to protect surface proteins of bacteria and viruses in vaccine discovery studies and preliminary results demonstrate its protective efficacy when administered to mice prior to exposureWe propose to determine whether or not MDP can protect mice from lethal irradiation when administered startingordays following irradiationFurtherwe propose to examine the protective efficacy of MDP on organ tissues and the immune systemSuccessful conclusion of this SBIR Phase I project will lead to continued develop through a potential Phase II and then IND enabling studies