Treatment of radiation disorders

Abstract

The present invention provides methods and compositions for the treatment of DNA damage related disorders. One embodiment is a method for the inhibition of side effects associated with chemotherapeutic and radiotherapeutic agents using chloroquine compounds. Another embodiment is a method for treatment and/or prevention of lethal or sub-lethal radiation toxicities associated with terrorist acts or war.

1 . A method of treatment for a radiation related disorder comprising administering to an animal subject in need thereof an effective amount of a chloroquine compound.  
     
     
         2 . The method of  claim 1  wherein said radiation related disorder is caused by an exposure to a non-ionizing radiation.  
     
     
         3 . The method of  claim 1  wherein said radiation related disorder is caused by an exposure to an ionizing radiation.  
     
     
         4 . The method of  claim 3  wherein said chloroquine compound treats a skin damage symptom caused by said ionizing radiation.  
     
     
         5 . The method of  claim 4  wherein said skin damage symptom is at least one symptom selected from swelling, itching, redness of skin, and hair loss.  
     
     
         6 . The method of  claim 3  wherein said chloroquine compound treats a non-skin damage symptom caused by said ionizing radiation.  
     
     
         7 . The method of  claim 6  wherein said non-skin damage symptom is at least one symptom selected from nausea, vomiting, diarrhea, loss of appetite, fatigue, fever, diminished organ function, seizures, cancer, and coma.  
     
     
         8 . The method of  claim 1  wherein said radiation related disorder is acute radiation syndrome.  
     
     
         9 . The method of  claim 1  wherein said chloroquine compound prevents a death due to radiation exposure.  
     
     
         10 . The method of  claim 1  wherein said chloroquine compound protects from sub-lethal and/or unintentional radiation exposure.  
     
     
         11 . The method of  claim 1  wherein said chloroquine compound protects from sub-lethal and/or lethal intentional radiation exposure.  
     
     
         12 . The method of  claim 11  wherein said intentional radiation exposure is due to an act of terrorism.  
     
     
         13 . A method of treatment for an adverse effect of a radiation therapy comprising administering to an animal subject in need thereof an effective amount of a chloroquine compound.  
     
     
         14 . The method of  claim 13  wherein said adverse effect is at least one effect selected from a skin damage, alopecia, or neutropenia.  
     
     
         15 . The method of  claim 1  or  13  wherein said chloroquine compound is at least one compound selected from chloroquine, chloroquine phosphate, hydroxychloroquine, chloroquine diphosphate, chloroquine sulphate, hydroxychloroquine sulphate, or enantiomers, derivatives, analogs, metabolites, pharmaceutically acceptable salts, and mixtures thereof.  
     
     
         16 . The method of  claim 15  wherein said compound is at least one compound selected from chloroquine, chloroquine phosphate, hydroxychloroquine, chloroquine diphosphate.  
     
     
         17 . The method of  claim 16  wherein said compound is chloroquine.  
     
     
         18 . The method of  claim 16  wherein said compound is hydroxychloroquine.  
     
     
         19 . The method of  claim 17  or  18  wherein said compound is an essentially pure (+) isomer.  
     
     
         20 . The method of  claim 17  or  18  wherein said compound is an essentially pure (−) isomer.  
     
     
         21 . The method of  claim 1  or  13  wherein the amount of the compound administered is at least about 0.1 mg/kg/day.  
     
     
         22 . The method of  claim 1  or  13  wherein the amount of the compound administered is up to about 10 mg/kg/day.  
     
     
         23 . The method of  claim 1  or  13  wherein the amount of the compound administered is more than about 0.1 mg/kg/day.  
     
     
         24  The method of  claim 1  or  13  wherein the amount of the compound administered is more than about 1.0 mg/kg/day.  
     
     
         25 . The method of  claim 1  or  13  wherein the amount of the compound administered is less than about 50 mg/kg/day.  
     
     
         26 . The method of  claim 1  or  13  wherein the amount of the compound administered is less than about 10 mg/kg/day.  
     
     
         27 . The method of  claim 1  or  13  wherein the chloroquine compound is administered more than once a week.  
     
     
         28 . The method  claim 1  or  13  wherein the chloroquine compound is administered daily, every two weeks, or once a month.  
     
     
         29 . The method of  claim 1  or  13  wherein the chloroquine compound is formulated in a sustained release formulation.  
     
     
         30 . The method of  claim 1  or  13  wherein said amount of said compound administered is about 0.1 to about 9 mg/kg once a week.