Treatment of Acute Radiation Syndrome using PIF, a Natural Immune Modulator

DESCRIPTION provided by applicant Recent nuclear accidents and threats have highlighted the growing risk of widespread radiation exposure causing a potentially devastating public health emergency Acute radiation syndrome ARS develops after total body or partial body irradiation at a moderate to high dose and is especially damaging to the immune system Damage to the skin gut and central nervous system is also common Accordingly complex injuries such as burns multi organ injury and trauma increase the death rate from acute radiation syndrome Despite advances in understanding the biological basis of radiation injury medications that effectively treat radiation injury are limited Medical management of accidentally irradiated victims remains based on treatment with immune factors that enhance renewal of immune cells In more severe cases a bone marrow transplant may be performed but complications from graft immune rejection limit the utility of this approach Furthermore existing treatments have limited efficacy are difficult to administer and are expensive to produce Therefore there is an urgent need to develop new drugs to treat acute radiation syndrome that are both effective and easy to deploy in an emergency radiation exposure scenario The goal of this proposal is to test the ability of synthetic PreImplantation Factor sPIF a natural immune regulatory peptide to reverse ARS in mice when treatment begins hours after exposure to various levels of radiation The survival and health of mice will be monitored and blood marker profiles will be performed Additionally details of the molecular basis of radiation damage and sPIFandapos s protective effects on the immune system will be examined Specifically mice tissues will be scored for inflammation and organ damage The types of immune cells present and the expression of inflammatory markers and immune regulators will be determined The purpose of these studies will be to advance the development of sPIF as a treatment for ARS and to collect the necessary data for the submission of an investigational new drug IND application The use of sPIF could revolutionize the treatment of ARS Preclinical studies have demonstrated that sPIF completely protected mice from death when administered hrs following lethal radiation exposure Significantly the sPIF treated mice also maintained normal blood markers indicating sPIFandapos s underlying protective effect on immune function Additional studies showed sPIF accelerated recovery of white blood cells when administered hours following sub lethal radiation exposure Significantly this project will more fully evaluate sPIFandapos s potential as a non toxic effective treatment for radiation exposure that could be easily deployed during a public health emergency PUBLIC HEALTH RELEVANCE This project addresses the public need for an effective easily administered drug that increases survival following exposure to radiation Currently survival of radiation exposure from nuclear accidents or weapons mostly depends on the strength and distance of the radiation because available medical treatments are not able to sufficiently prevent and repair damage Therefore development of an effective drug to treat acute radiation syndrome that can be mass produced stored and easily administered during a radiation emergency has significant impacts on public health This project will build upon promising preliminary data to more fully evaluate the potential for synthetic Preimplantation Factor a natural immune regulatory peptide to serve as a non toxic effective treatment for radiation exposure