Compositions and methods for treating acute radiation syndrome

Abstract

Embodiments are directed to a method of treating acute radiation syndrome comprising administering to a subject following exposure to radiation a PIF peptide. Some embodiments describe a method of treating acute radiation syndrome following radiation exposure comprising transplanting bone marrow that has been exposed to a PIF peptide prior to transplantation into a subject. Other embodiments describe a method of increasing engraftment of a transplanted organ, tissue, or cell by pre-exposing the organ, tissue, or cell to a PIF peptide.

What is claimed is: 
     
         1 . A method of treating and/or preventing acute radiation syndrome in a subject in need thereof following exposure to radiation comprising administering to the subject a pharmaceutical composition comprising (i) a therapeutically effective amount of a PreImplantation Factor (PIF) peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, and (ii) a pharmaceutically acceptable carrier, wherein the subject does not receive a bone marrow transplant and
 wherein the mimetics thereof comprise MVRIKPGSA and one or a plurality of side chain modifications, are from 9 to 18 amino acids in length and share the same or similar desired biological activity of the PIF peptide.   
     
     
         2 . The method of  claim 1 , wherein the therapeutically effective amount is from about 0.10 milligrams/kilograms/day to about 10.00 milligrams/kilograms/day. 
     
     
         3 . The method of  claim 1 , wherein the therapeutically effective amount is from about 0.75 milligrams/kilograms/day to about 1.50 milligrams/kilograms/day. 
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount is from about 0.75 milligrams/kilograms/day to about 1.00 milligrams/kilograms/day. 
     
     
         5 . The method of  claim 1 , wherein the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, is administered within about 24 hours after exposure to radiation. 
     
     
         6 . The method of  claim 1 , wherein the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, is administered intermittently or continuously for a time period of from about 2 to about 14 days. 
     
     
         7 . The method of  claim 1 , wherein the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, is administered intermittently, with about 1 dose per day or about 1 dose every two days for at least about twelve weeks. 
     
     
         8 . The method of  claim 1 , wherein the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, is administered intravenously, intramuscularly, or subcutaneously. 
     
     
         9 . The method of  claim 1 , wherein the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, is administered in an intermittent or continuous infusion. 
     
     
         10 . The method of  claim 1 , wherein the acute radiation syndrome is caused by exposure to lethal radiation. 
     
     
         11 . The method of  claim 1 , wherein the acute radiation syndrome is caused by exposure to a radiation dose of about 100 rads to about 6000 rads. 
     
     
         12 . The method of  claim 1 , wherein the acute radiation syndrome comprises delayed effects of acute radiation exposure, including and/or damage to any organ, tissue, or cell. 
     
     
         13 . The method of  claim 1 , wherein the PIF peptide comprises one or a combination of an amino acid sequence comprising at least 86% sequence homology with: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, or SEQ ID NO: 29. 
     
     
         14 . The method of  claim 1 , wherein the administration of the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof restores colon morphology or colon crypt cell morphology, and/or reverses colon injury in said subject. 
     
     
         15 . The method of  claim 1 , wherein the acute radiation syndrome is caused by exposure to sub-lethal radiation. 
     
     
         16 . The method of  claim 1 , wherein the PIF peptide is SEQ ID NO:13. 
     
     
         17 . A method of treating gastrointestinal (GI) tract damage associated with acute radiation syndrome in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising (i) a therapeutically effective amount of a PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, and (ii) a pharmaceutically acceptable carrier, wherein the subject does not receive a bone marrow transplant, and wherein the mimetics thereof comprise MVRIKPGSA and one or a plurality of side chain modifications, are from 9 to 18 amino acids in length and share the same or similar desired biological activity of the PIF peptide. 
     
     
         18 . The method of  claim 17 , wherein the therapeutically effective amount of the PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, is from about 0.10 milligrams/kilograms/day to about 10.00 milligrams/kilograms/day. 
     
     
         19 . The method of  claim 17 , wherein the PIF peptide comprises one or a combination of an amino acid sequence comprising at least 86% sequence homology with: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, or SEQ ID NO: 29. 
     
     
         20 . A method of reversing colon injury in a subject treated with radiation comprising administering to the subject a pharmaceutical composition comprising (i) a therapeutically effective amount of a PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof, and (ii) a pharmaceutically acceptable carrier, wherein the subject does not receive a bone marrow transplant and
 wherein the mimetics thereof comprise MVRIKPGSA and one or a plurality of side chain modifications, are from 9 to 18 amino acids in length and share the same or similar desired biological activity of the PIF peptide.