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.

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 therapeutically effective amount of a PIF peptide, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject does not receive a bone marrow transplant. 
     
     
         3 . 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. 
     
     
         4 . 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. 
     
     
         5 . 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. 
     
     
         6 . The method of  claim 1 , wherein the PIF peptide is administered within about 24 hours after exposure to radiation. 
     
     
         7 . The method of  claim 1 , wherein the PIF peptide is administered intermittently or continuously for a time period of from about 2 to about 14 days. 
     
     
         8 . The method of  claim 1 , wherein, if the PIF peptide is administered intermittently, the dosing regimen comprises about 1 dose per day or about 1 dose every two days for at least about twelve weeks. 
     
     
         9 . The method of  claim 1 , wherein the PIF peptide is administered intravenously, intramuscularly, or subcutaneously. 
     
     
         10 . The method of  claim 1 , wherein the PIF peptide is administered in an intermittent or continuous infusion. 
     
     
         11 . The method of  claim 1 , wherein the acute radiation syndrome is caused by exposure to lethal or sub-lethal radiation. 
     
     
         12 . 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. 
     
     
         13 . The method of  claim 1 , wherein the acute radiation syndrome comprises delayed effects of acute radiation exposure, including damage to any organ, tissue, or cell. 
     
     
         14 . The method of  claim 1 , wherein the PIF peptide comprises one or a combination of an amino acid sequence having 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: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, 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, SEQ ID NO: 29, mimetics thereof, and pharmaceutically acceptable salts thereof. 
     
     
         15 .- 40 . (canceled) 
     
     
         41 . A method of treating and/or preventing acute radiation syndrome following radiation exposure comprising transplanting one or a plurality of bone marrow cells into a subject in need thereof, wherein the one or plurality of bone marrow cells is pre-exposed to a therapeutically effective amount of PIF peptide prior to transplantation, and the PIF peptide comprises or consists of an amino acid sequence having at least 86% sequence homology to an amino acid sequence selected from: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, 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, SEQ ID NO: 29, mimetics thereof, and pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         42 .- 44 . (canceled) 
     
     
         45 . The method of  claim 41 , wherein the therapeutically effective amount of PIF peptide is from about 0.10 milligrams/kilograms/day to about 10.00 milligrams/kilograms/day. 
     
     
         46 . The method of  claim 41 , wherein the one or a plurality of bone marrow cells is pre-exposed to a concentration of PIF peptide for a time period and under conditions sufficient to pre-condition the bone marrow cells prior to transplantation and/or stimulate cortisol secretion. 
     
     
         47 .- 49 . (canceled) 
     
     
         50 . A method of treating and/or preventing adult or juvenile type I or type II diabetes comprising transplanting one or a plurality of pancreatic islet cells into a subject in need thereof, wherein the islet cells are pre-exposed to a therapeutically effective amount of PIF peptide prior to transplantation, and wherein the PIF peptide comprises or consists of an amino acid sequence having 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: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, 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, SEQ ID NO: 29, mimetics thereof, pharmaceutically acceptable salts thereof, or combinations thereof. 
     
     
         51 . The method of  claim 50 , wherein the subject has juvenile Type I diabetes. 
     
     
         52 . The method of  claim 50 , wherein the subject has adult Type I diabetes. 
     
     
         53 . (canceled) 
     
     
         54 . The method of  claim 50 , wherein the one or a plurality of pancreatic islet cells is pre-exposed to a concentration of PIF peptide for a time period and under conditions sufficient to stimulate cortisol and/or insulin secretion of the pancreatic islet cells prior to transplantation. 
     
     
         55 . (canceled) 
     
     
         56 . The method of  claim 50 , wherein the one or plurality of pancreatic islet cells is pre-exposed to a concentration of one or a combination of PIF peptides from about 10 nM to about 1000_ nM for about 1 hour to about 4 hours. 
     
     
         57 . (canceled) 
     
     
         58 . A method of increasing the likelihood of successful engraftment of a transplanted organ, tissue, or cells comprising transplanting an organ, tissue, or cell into a subject in need thereof, wherein the organ, tissue, or cell is exposed to a PIF peptide prior to transplantation, wherein the PIF peptide comprises or consists of an amino acid sequence having at least 86% sequence homology to an amino acid sequence chosen from: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, 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, SEQ ID NO: 29, mimetics thereof, and pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         59 . The method of  claim 58 , wherein the transplantation is a bone marrow transplant, pancreatic islet cell transplant, adrenal cell transplant, or heart transplant. 
     
     
         60 .- 63 . (canceled) 
     
     
         64 . The method of  claim 58 , wherein the one or a plurality of organ, tissue, or cells is exposed to a concentration of PIF peptide for a time period and under conditions sufficient to pre-condition the organ, tissue, or cells for transplantation prior to transplantation. 
     
     
         65 .- 66 . (canceled) 
     
     
         67 . The method of  claim 58 , wherein the one or plurality of pancreatic islet cells is pre-exposed to a concentration of one or a combination of PIF peptides from about 10 nM to about 1000_ nM for about 1 hour to about 4 hours. 
     
     
         68 . (canceled) 
     
     
         69 . The method of  claim 58 , wherein the organ, tissue, or cells are selected from one or a combination of organs chosen from: bone marrow, skin, adrenal gland, pancreas, heart, lung, kidney, spleen, and liver. 
     
     
         70 . A method of increasing the viability of an organ, tissue, or cell prior to its transplantation into a subject in need of transplantation comprising treating the organ, tissue or cell with a therapeutically effective amount of PIF peptide prior to transplantation, wherein the PIF peptide comprises or consists of an amino acid sequence having at least 86% sequence homology to an amino acid sequence chosen from: SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, 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, SEQ ID NO: 29, mimetics thereof, and pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         71 . A method of increasing the likelihood of acceptance of a transplant of a donor organ, tissue, or cell into a subject, the method comprising exposing the organ, tissue or cell to one or more compositions comprising at least one PIF peptide or a mutant thereof or a pharmaceutically acceptable salt thereof prior to transplanting the organ, tissue, or cell into the subject. 
     
     
         72 .- 98 . (canceled)