COMPOSITIONS AND METHODS FOR TREATING ACUTE RADIATION SYNDROME
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)