Control of radiation injury

Abstract

The invention relates to the field of drug development against acute radiation injury caused by exposure to high-energy electromagnetic waves (X-rays, gamma rays) or particles (alpha particles, beta particles, neutrons). To date, there is no effective drug to ameliorate radiation injury after accidental exposure to ionizing irradiation. The invention provides a method of treating radiation injury of a subject in need thereof comprising administering to the subject a peptide, or functional analogue or derivative thereof, of smaller than 30 amino acids. Furthermore, the invention provides use of a peptide, or functional analogue or derivative thereof, of smaller than 30 amino acids for the production of a pharmaceutical composition for the treatment of a subject suffering from or believed to be suffering from radiation injury. In particular, the invention provides anti-radiation peptides having a dose reduction factor (DRF) against acute gamma irradiation of at least 1.10, said DRF determinable by testing which dose of radiation results in 50% mortality at 30 days (LD50/30) after whole body radiation (WBI) in a test group of mice treated with said peptide at 72 hours after WBI and, testing which dose of radiation results in 50% mortality at 30 days (LD50/30) after whole body radiation (WBI) in a control group of mice treated only with the vehicle of said peptide at 72 hours after WBI and wherein the DRF is calculated by dividing the LD50/30 of the peptide-treated animals by the LD50/30 of the vehicle-treated animals.

1 . A method of treating a subject suffering from or believed to be suffering from radiation injury, said method comprising:
 providing the subject with a pharmaceutical composition comprising: means for treating or preventing radiation injury and a pharmaceutically acceptable excipient.   
     
     
         2 . The method according to  claim 1  wherein the means for treating or preventing radiation injury comprises a peptide, or functional analogue or derivative thereof, of smaller than 30 amino acids. 
     
     
         3 . The method according to  claim 2  wherein the peptide is smaller than fifteen (15) amino acids. 
     
     
         4 . The method according to  claim 3 , wherein the peptide is smaller than seven (7) amino acids. 
     
     
         5 . The method according to  claim 4 , wherein the peptide consists of from two (2) to six (6) amino acids. 
     
     
         6 . The method according to  claim 5 , wherein the peptide consists of three (3) to five (5) amino acids. 
     
     
         7 . The method according to  claim 6 , wherein the peptide consists of 4 amino acids. 
     
     
         8 . The method according to  claim 1  wherein said radiation injury comprises acute radiation injury. 
     
     
         9 . The method according to  claim 1  wherein said radiation injury comprises damage of the lining of the intestinal tract of the subject involving gastrointestinal syndrome. 
     
     
         10 . The method according to  claim 2  wherein the peptide has a dose reduction factor (DRF) against acute gamma irradiation of at least 1.10, said DRF determinable by
 a. testing which dose of radiation results in 50% mortality at 30 days (LD50/30) after whole body radiation (WBI) in a test group of mice treated with the peptide at 72 hours after WBI and, 
 b. testing which dose of radiation results in 50% mortality at 30 days (LD50/30) after whole body radiation (WBI) in a control group of mice treated only with the vehicle of the peptide at 72 hours after WBI and, 
 c. wherein the DRF is calculated by dividing the LD50/30 of the peptide-treated animals by the LD50/30 of the vehicle-treated animals. 
 
     
     
         11 . The method according to  claim 10  wherein the peptide has a dose reduction factor (DRF) of at least 1.20 or at least 1.25. 
     
     
         12 . The method according to  claim 1  wherein said radiation injury is irradiation injury. 
     
     
         13 . The method according to  claim 2  wherein said method of treating comprises subcutaneous or intramuscular injection of the peptide into the subject. 
     
     
         14 . The method according to  claim 13  wherein the peptide is contained within an autoinjector. 
     
     
         15 . An autoinjector for administering a parenteral composition, the improvement comprising, including in said autoinjector, adapted for injection, means for treating or preventing radiation injury. 
     
     
         16 . The autoinjector of  claim 15 , wherein the means for treating or preventing radiation injury comprises a peptide, or functional analogue or derivative thereof, of smaller than thirty (30) amino acids. 
     
     
         17 . The autoinjector of  claim 16  wherein the means for treating or preventing radiation injury comprises a peptide, the peptide being smaller than fifteen (15) amino acids. 
     
     
         18 . The autoinjector of  claim 17  wherein the peptide is smaller than seven (7) amino acids. 
     
     
         19 . The autoinjector of  claim 18  wherein the peptide consists of from two (2) to six (6) amino acids. 
     
     
         20 . The autoinjector of  claim 19 , wherein the peptide consists of from three (3) to five (5) amino acids. 
     
     
         21 . The autoinjector of  claim 20  wherein the peptide consists of four (4) amino acids. 
     
     
         22 . The autoinjector of  claim 16  wherein the radiation injury comprises acute radiation injury. 
     
     
         23 . The autoinjector of  claim 16  wherein said radiation injury comprises damage of the lining of the intestinal tract of said subject, the so-called gastrointestinal syndrome. 
     
     
         24 . The autoinjector of  claim 16  wherein the peptide has a dose reduction factor (DRF) against acute gamma irradiation of at least 1.10, said DRF determinable by
 a. testing which dose of radiation results in 50% mortality at 30 days (LD50/30) after whole body radiation (WBI) in a test group of mice treated with the peptide at 72 hours after WBI and, 
 b. testing which dose of radiation results in 50% mortality at 30 days (1.1)50/30) after whole body radiation (WBI) in a control group of mice treated only with the vehicle of the peptide at 72 hours after WBI and, 
 c. wherein the DRF is calculated by dividing the LD50/30 of the peptide-treated animals by the LD50/30 of the vehicle-treated animals. 
 
     
     
         25 . The autoinjector of  claim 24  wherein the peptide has a DRF of at least 1.20 or at least 1.25. 
     
     
         26 . The autoinjector of  claim 16  wherein said radiation injury is irradiation injury. 
     
     
         27 . The autoinjector of  claim 16  wherein said radiation is emitted by radioactive substances.