Treatment of DNA damage related disorders

Abstract

The present invention provides methods and compositions for prophylaxis and treatment of a variety of disorders including DNA damage related disorders, cancer, ischemia, oxidative stress, atherosclerosis, and stroke using a chloroquine compound.

1 . A method of prophylaxis of lymphoma comprising administering to a subject at risk of lymphoma, an effective amount of a chloroquine compound.  
     
     
         2 . (canceled)  
     
     
         3 . (canceled)  
     
     
         4 . (canceled)  
     
     
         5 . (canceled)  
     
     
         6 . (canceled)  
     
     
         7 . The method of  claim 1 , further comprising monitoring the subject for development of lymphoma after administration of the chloroquine compound.  
     
     
         8 . (canceled)  
     
     
         9 . The method of  claim 7 , wherein the monitoring comprises taking a sample of a body fluid, or performing a scan of an internal organ.  
     
     
         10 . The method of  claim 1 , wherein the subject is at risk of lymphoma by having a precancerous tissue.  
     
     
         11 . (canceled)  
     
     
         12 . (canceled)  
     
     
         13 . (canceled)  
     
     
         14 . (canceled)  
     
     
         15 . (canceled)  
     
     
         16 . The method of  claim 1 , wherein the subject is at risk of lymphoma due to a genetic variation associated with increased risk of lymphoma.  
     
     
         17 . The method of  claim 1 , wherein the subject is at risk of lymphoma due to viral infection.  
     
     
         18 . The method of  claim 1 , wherein the subject is at risk of lymphoma due to exposure to a carcinogen or irradiation.  
     
     
         19 . The method of  claim 1 , wherein the subject is at risk of lymphoma due to exposure to X-rays.  
     
     
         20 . The method of  claim 1 , further comprising determining presence of a genetic variation in an ATM gene of the subject associated with lymphoma.  
     
     
         21 . The method of  claim 1 , further comprising administering a chemopreventive agent other than the chloroquine compound to the subject.  
     
     
         22 . The method of  claim 1 , further comprising determining the risk of lymphoma in the subject before administering the chloroquine compound.  
     
     
         23 . The method of  claim 1 , wherein the chloroquine compound is administered intravenously.  
     
     
         24 . The method of  claim 1 , wherein the chloroquine compound is administered orally.  
     
     
         25 . (canceled)  
     
     
         26 . (canceled)  
     
     
         27 . The method of  claim 1 , wherein the prophylaxis is effective to prevent detectable development of lymphoma for at least six months after administering the effective dosage.  
     
     
         28 . The method of  claim 1 , wherein the administering is performed before exposure of the subject to the risk of lymphoma.  
     
     
         29 . The method of  claim 1 , wherein the administering is performed at regular intervals for a period of at least six months.  
     
     
         30 . The method of  claim 1 , wherein the chloroquine compound is selected from the group consisting of chloroquine, chloroquine phosphate, hydroxychloroquine, chloroquine diphosphate, chloroquine sulphate, hydroxychloroquine sulphate, or enantiomers, derivatives, analogs, metabolites, pharmaceutically acceptable salts, and mixtures thereof.  
     
     
         31 . The method of  claim 30 , wherein the compound is chloroquine, chloroquine phosphate or chloroquine diphosphate.  
     
     
         32 . The method of  claim 1 , wherein the chloroquine compound has a systemic effect.  
     
     
         33 . The method of  claim 1 , wherein the patient is human and the dosage is 0.05 to 1 mg/kg per day.  
     
     
         34 . The method of  claim 1 , wherein the patient is human and the dosage is 0.2 to 0.6 mg/kg per day.  
     
     
         35 . The method of  claim 34 , wherein the patient has been exposed to a carcinogen or radiation, and the dosage is administered at least on the day of exposure and the day following exposure.  
     
     
         36 . The method of  claim 34 , wherein the patient has been exposed to a carcinogen or radiation, and the dosage is administered at least on the day before the exposure, on the day of the exposure, and at least on the day following the exposure.  
     
     
         37 . The method of  claim 1 , wherein the patient is human and has genetic susceptibility to cancer, and the dosage is 0.2 to 0.6 mg/kg week.  
     
     
         38 . The method of  claim 1 , wherein the amount of the compound administered is up to about 10 mg/kg/day.  
     
     
         39 . The method of  claim 1 , wherein the amount of the compound administered is more than about 0.1 mg/kg/day.  
     
     
         40 . The method of  claim 1 , wherein the amount of the compound administered is more than about 1.0 mg/kg/day.  
     
     
         41 . The method of  claim 1 , wherein the amount of the compound administered is less than about 50 mg/kg/day.  
     
     
         42 . The method of  claim 1 , wherein the amount of the compound administered is less than about 10 mg/kg/day.  
     
     
         43 . The method of  claim 1 , wherein the chloroquine compound is administered more than once a week.  
     
     
         44 . The method  claim 1 , wherein the chloroquine compound is administered daily.  
     
     
         45 . The method of  claim 1 , wherein the chloroquine compound is formulated in a sustained release formulation.  
     
     
         46 . The method of  claim 1 , wherein the subject is human.  
     
     
         47 . A method of therapeutically treating lymphoma comprising administering to a subject having lymphoma, an effective amount of a chloroquine compound whereby the lymphoma is therapeutically treated.  
     
     
         48 . (canceled)  
     
     
         49 . (canceled)  
     
     
         50 . The method of  claim 47 , wherein the treatment reduces or eliminates further growth of the lymphoma.  
     
     
         51 . The method of  claim 47 , wherein the treatment shrinks or eliminates the lymphoma tumor.  
     
     
         52 . The method of  claim 47 , wherein the treatment inhibits invasion of the lymphoma into tissues of the subject and/or inhibits metastasis of the lymphoma.  
     
     
         53 . The method of  claim 47 , further comprising monitoring changes in the lymphoma responsive to the administering.  
     
     
         54 . The method of  claim 53 , wherein the monitoring comprising taking a sample of a body fluid, or performing a scan of an internal organ.  
     
     
         55 . The method of  claim 47 , further comprising identifying a genetic variation in an ATM gene of the subject associated with lymphoma.  
     
     
         56 . The method of  claim 47 , further comprising administering a chemotherapeutic agent other than the chloroquine compound to the subject.  
     
     
         57 . The method of  claim 47 , further comprising determining presence of the lymphoma before the administering step.  
     
     
         58 . (canceled)  
     
     
         59 . The method of  claim 47 , wherein the patient is human and the dosage is 0.05 to 1 mg/kg per week.  
     
     
         60 . The method of  claim 1 , wherein the patient is human and the dosage is 0.2 to 0.6 mg/kg per day.  
     
     
         61 . The method of  claim 47 , wherein the subject is free of psoriasis, malaria, protozoal infections, Alzheimer's disease, Parkinson's disease, lupus erythematosus, rheumatism, hypercalcemia, multiple sclerosis, and migraine.