Methods of treating DNA damage

9,987,302

14/236756

August 08, 2012

The present invention relates to methods and compositions of treating patients suffering from, or at risk for, DNA damage and to increase life span, i.e., prevent or slow the aging process in all species. The treatment includes administering to the patient a pharmaceutical composition that includes carbon monoxide.

Otterbein, Leo E. (Beverly, MA, US)

Beth Israel Deaconess Medical Center, Inc. (Boston, MA, US)

1. A method of reducing radiation-induced DNA damage in a subject, the method comprising: administering to a subject whose substantially whole body has been exposed to an acute dose of a DNA-damaging level of ionizing radiation, and who exhibits symptoms of radiation-induced DNA damage, a pharmaceutical composition comprising an amount of carbon monoxide effective to reduce radiation-induced DNA damage in the subject, the pharmaceutical composition being administered intermittently or continuously until the subject no longer exhibits symptoms of DNA damage.

2. The method of claim 1 , wherein the ionizing radiation is from a nuclear reactor or nuclear weapon.

3. The method of claim 1 , wherein the pharmaceutical composition is in gaseous form and is administered to the subject by inhalation.

4. The method of claim 1 , wherein the pharmaceutical composition is in liquid form and is administered to the subject orally.

5. The method of claim 1 , wherein the acute dose of ionizing radiation is at least one Gray.

6. The method of claim 1 , wherein the pharmaceutical composition is administered directly to the abdominal cavity of the subject.

7. The method of claim 1 , wherein the pharmaceutical composition comprises a carbon monoxide-releasing compound.

8. The method of claim 1 , wherein the pharmaceutical composition is administered by an artificial lung.

9. The method of claim 1 , wherein the pharmaceutical composition is administered by an extracorporeal membrane gas exchange device.

10. The method of claim 1 , wherein the pharmaceutical composition is administered for about 1, 2, 3, 5, or 6 months.

11. The method of claim 1 , wherein the pharmaceutical composition is administered to the subject immediately after the subject being exposed to ionizing radiation.

12. The method of claim 1 , wherein the pharmaceutical composition is administered to the subject by acute administration.

13. The method of claim 1 , wherein the method induces DNA repair process.

14. A method of reducing DNA damage in a subject during warfare or an act of terrorism, the method comprising: administering to a subject who has been exposed to DNA-damaging levels of radiation from an explosion of a nuclear weapon and who exhibits symptoms of radiation-induced DNA damage, a pharmaceutical composition comprising an amount of carbon monoxide effective to reduce DNA damage in the subject, the pharmaceutical composition being administered intermittently or continuously until the subject no longer exhibits symptoms of DNA damage.

15. The method of claim 14 , wherein the pharmaceutical composition is in gaseous form and is administered to the subject by inhalation.

16. The method of claim 14 , wherein the pharmaceutical composition is in liquid form and is administered to the subject orally.

17. The method of claim 14 , wherein the pharmaceutical composition is administered directly to the abdominal cavity of the subject.

18. The method of claim 14 , wherein the pharmaceutical composition comprises a carbon monoxide-releasing compound.

19. The method of claim 14 , wherein the pharmaceutical composition is administered by an artificial lung.

20. The method of claim 14 , wherein the pharmaceutical composition is administered by an extracorporeal membrane gas exchange device.

21. The method of claim 14 , wherein the pharmaceutical composition is administered for about 1, 2, 3, 5, or 6 months.

22. The method of claim 14 , wherein the pharmaceutical composition is administered to the subject immediately after the subject being exposed to radiation.

23. The method of claim 14 , wherein the pharmaceutical composition is administered to the subject by acute administration.

24. The method of claim 14 , wherein the method induces DNA repair process.

25. A method of reducing hyperthermia-induced DNA damage in a subject, the method comprising: identifying a subject whose whole body has been exposed to DNA-damaging levels of hyperthermia, and who exhibits symptoms of hyperthermia-induced DNA damage; and administering to the subject a pharmaceutical composition comprising an amount of carbon monoxide effective to reduce hyperthermia-induced DNA damage in the subject, the pharmaceutical composition being administered intermittently or continuously until the subject no longer exhibits symptoms of DNA damage.

26. The method of claim 25 , wherein the pharmaceutical composition is in gaseous form and is administered to the subject by inhalation.

27. The method of claim 25 , wherein the pharmaceutical composition is in liquid form and is administered to the subject orally.

28. The method of claim 25 , wherein the pharmaceutical composition is administered directly to the abdominal cavity of the subject.

29. The method of claim 25 , wherein the pharmaceutical composition comprises a carbon monoxide-releasing compound.

30. The method of claim 25 , wherein the pharmaceutical composition is administered by an artificial lung.

31. The method of claim 25 , wherein the pharmaceutical composition is administered by an extracorporeal membrane gas exchange device.

32. The method of claim 25 , wherein the pharmaceutical composition is administered for about 1, 2, 3, 5, or 6 months.

33. A method of treating acute radiation syndrome in a subject, the method comprising: administering to a subject whose substantially whole body has been exposed to an acute dose of a DNA-damaging level of ionizing radiation, and who is diagnosed as having acute radiation syndrome, a pharmaceutical composition comprising an amount of carbon monoxide effective to reduce radiation-induced DNA damage in the subject, the pharmaceutical composition being administered intermittently or continuously until the subject no longer exhibits symptoms of DNA damage.

34. The method of claim 33 , wherein the ionizing radiation is from a nuclear reactor or nuclear weapon.

35. The method of claim 33 , wherein the acute dose of ionizing radiation is at least one Gray.

36. The method of claim 33 , wherein the pharmaceutical composition is in gaseous form and is administered to the subject by inhalation.

37. The method of claim 33 , wherein the pharmaceutical composition is in liquid form and is administered to the subject orally.

38. The method of claim 33 , wherein the pharmaceutical composition is administered directly to the abdominal cavity of the patient.

39. The method of claim 33 , wherein the pharmaceutical composition comprises a carbon monoxide-releasing compound.

40. The method of claim 33 , wherein the pharmaceutical composition is administered by an artificial lung.

41. The method of claim 33 , wherein the pharmaceutical composition is administered by an extracorporeal membrane gas exchange device.

42. The method of claim 33 , wherein the pharmaceutical composition is administered for about 1, 2, 3, 5, or 6 months.

43. The method of claim 33 , wherein the pharmaceutical composition is administered to the subject immediately after the subject being exposed to ionizing radiation.

44. The method of claim 33 , wherein the pharmaceutical composition is administered to the subject by acute administration.

45. The method of claim 33 , wherein the method induces DNA repair process.

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