Sdf-1 delivery for treating ischemic tissue

Abstract

A method of treating a cardiomyopathy in a subject includes administering directly to or expressing locally in a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject an amount of SDF-1 effective to cause functional improvement in at least one of the following parameters: left ventricular volume, left ventricular area, left ventricular dimension, cardiac function, 6-minute walk test, or New York Heart Association (NYHA) functional classification.

1 .- 40 . (canceled) 
     
     
         41 . A method of treating a myocardial infarction in a large mammal comprising:
 administering SDF-1 plasmid to the peri-infarct region of the mammal by catheterization, SDF-1 being expressed from the peri-infarct region at an amount effective to cause functional improvement in at least one of the following parameters: left ventricular volume, left ventricular area, left ventricular dimension, cardiac function, 6-minute walk test, or New York Heart Association (NYHA) functional classification.   
     
     
         42 . The method of  claim 41 , the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to cause functional improvement in left ventricular end systolic volume, left ventricular ejection fraction, wall motion score index, left ventricular end diastolic length, left ventricular end systolic length, left ventricular end diastolic area, left ventricular end systolic area, or left ventricular end diastolic volume. 
     
     
         43 . The method of  claim 42 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to improve left ventricular end systolic volume. 
     
     
         44 . The method of  claim 42 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to improve left ventricular ejection fraction. 
     
     
         45 . The method of  claim 43 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to improve left ventricular end systolic volume by at least about 10%. 
     
     
         46 . The method of  claim 44 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to improve left ventricular ejection fraction by at least about 10%. 
     
     
         47 . The method of  claim 41 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to improve 6 minute walk distance by at least about 30 meters or improve NYHA class by at least 1 class. 
     
     
         48 . The method of  claim 41 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to improve left ventricular end systolic volume by at least about 10%, improve left ventricular ejection fraction by at least about 10%, improve wall motion score index by about 5%, improve 6 minute walk distance by at least about 30 meters, and improve NYHA class by at least 1 class. 
     
     
         49 . The method of  claim 41 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to substantially improve vasculogenesis of the weakened, ischemic, and/or peri-infarct region. 
     
     
         50 . The method of  claim 49 , wherein the amount of SDF-1 administered to the weakened, ischemic, and/or peri-infarct region is effective to increase vasculogenesis by at least 20% based on vessel density or measured by myocardial perfusion imaging with an improvement in summed rest score, summed stress score, and/or summed difference score of at least about 10%. 
     
     
         51 . The method of  claim 41 , wherein the SDF-1 is administered by injecting a solution comprising SDF-1 expressing plasmid DNA in the weakened, ischemic, and/or peri-infarct region and expressing SDF-1 from the weakened, ischemic, and/or peri-infarct region. 
     
     
         52 . The method of  claim 51 , wherein the SDF-1 is expressed from the weakened, ischemic, and/or peri-infarct region at an amount effective to improve left ventricular end systolic volume. 
     
     
         53 . The method of  claim 51 , wherein the SDF-1 plasmid is administered to the weakened, ischemic, and/or peri-infarct region in multiple injections of the solution with each injection comprising about 0.33 mg/ml to about 5 mg/ml of SDF-1 plasmid/solution. 
     
     
         54 . The method of  claim 53 , wherein each injection has a volume of at least about 0.2 ml. 
     
     
         55 . The method of  claim 54 , wherein the SDF-1 plasmid is administered to the weakened, ischemic, and/or peri-infarct region in at least about 10 injections. 
     
     
         56 . The method of  claim 55 , wherein the amount of SDF-1 plasmid administered to the weakened, ischemic, and/or peri-infarct region is great than about 4 mg. 
     
     
         57 . The method of  claim 55 , wherein the volume of solution of SDF-1 plasmid administered to the weakened, ischemic, and/or peri-infarct region is at least about 10 ml. 
     
     
         58 . The method of  claim 51 , wherein the SDF-1 plasmid is administered to the weakened, ischemic, and/or peri-infarct region in at least 10 injections of the solution with each injection comprising about 0.33 mg/ml to about 5 mg/ml of SDF-1 plasmid/solution and each injection has a volume of at least about 0.2 ml. 
     
     
         59 . The method of  claim 51 , wherein SDF-1 is expressed at a therapeutically effective amount in the weakened, ischemic, and/or peri-infarct region for greater than about three days. 
     
     
         60 . The method of  claim 41 , wherein the myocardial tissue of the subject is imaged to define the area of weakened, ischemic, and/or peri-infarct region prior to administration of the SDF-1 plasmid and the SDF-1 plasmid is administered to the weakened, ischemic, and/or peri-infarct region defined by the imaging. 
     
     
         61 . The method of  claim 60 , wherein the imaging includes at least one of echocardiography, magnetic resonance imaging, coronary angiogram, electroanatomical mapping, or fluoroscopy. 
     
     
         62 . A method of improving left ventricular end systolic volume in a large mammal after myocardial infarction comprising:
 injecting a solution comprising SDF-1 expressing plasmid DNA into the peri-infarct region of the mammal by catheterization, the SDF-1 being expressed from the peri-infarct region at an amount effective to cause functional improvement in left ventricular end systolic volume.   
     
     
         63 . The method of  claim 62 , wherein the amount of SDF-1 injected into the peri-infarct region is effective to improve left ventricular end systolic volume of at least about 10%. 
     
     
         64 . The method of  claim 62 , wherein the amount of SDF-1 injected into the peri-infarct region is effective to improve left ventricular ejection fraction by at least about 10%. 
     
     
         65 . The method of  claim 62 , wherein the amount of SDF-1 injected into the peri-infarct region is effective to improve 6 minute walk distance by at least about 30 meters or improve NYHA class by at least 1 class. 
     
     
         66 . The method of  claim 62 , wherein the amount of SDF-1 injected into the peri-infarct region is effective to improve left ventricular ejection fraction by at least about 10%, improve wall motion score index by about 5%, improve 6 minute walk distance by at least about 30 meters, and improve NYHA class by at least 1 class. 
     
     
         67 . The method of  claim 62 , wherein the SDF-1 plasmid solution is injected into the peri-infarct region in multiple injections of the solution with each injection comprising about 0.33 mg/ml to about 5 mg/ml of SDF-1 plasmid/solution. 
     
     
         68 . The method of  claim 67 , wherein each injection has a volume of at least about 0.2 ml. 
     
     
         69 . The method of  claim 68 , wherein the SDF-1 plasmid is administered to the peri-infarct region in at least about 10 injections. 
     
     
         70 . The method of  claim 69 , wherein the amount of SDF-1 plasmid administered to the peri-infarct region is great than about 4 mg. 
     
     
         71 . The method of  claim 70  wherein the volume of solution of SDF-1 plasmid administered to the peri-infarct region is at least about 10 ml. 
     
     
         72 . The method of  claim 62 , wherein the SDF-1 plasmid is injected into the peri-infarct region in at least 10 injections of the solution with each injection comprising about 0.33 mg/ml to about 5 mg/ml of SDF-1 plasmid/solution and each injection has a volume of at least about 0.2 ml. 
     
     
         73 . The method of  claim 62 , wherein the myocardial tissue of the subject is imaged to define the peri-infarct region prior to injection of the SDF-1 plasmid and the SDF-1 plasmid is injected into the peri-infarct region defined by the imaging. 
     
     
         74 . The method of  claim 73 , wherein the imaging includes at least one of echocardiography, magnetic resonance imaging, coronary angiogram, electroanatomical mapping, or fluoroscopy.