Sdf-1 delivery for treating advanced ischemic cardiomyopathy

Patent metadata

Field	Value
Publication number	US-2017049856-A1
Application number	US-201515305369-A
Country	US
Kind code	A1
Filing date	Apr 28, 2015
Priority date	Apr 28, 2014
Publication date	Feb 23, 2017
Grant date	—

Abstract

Provided herein are methods of treating a cardiomyopathy in a subject by 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. Methods of treating subjects with advanced ischemic cardiomyopathy are further disclosed herein.

First claim

1 . A method of treating a subject having advanced ischemic cardiomyopathy, the method comprising administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1.

2 . The method of claim 1 , wherein advanced ischemic cardiomyopathy is indicated by the subject having an end systolic volume of about 151 ml.

3 . The method of claim 1 , wherein advanced ischemic cardiomyopathy is indicated by the subject having a left ventricular ejection fraction (LVEF) of less than 35%.

4 . The method of claim 1 , wherein advanced ischemic cardiomyopathy is indicated by the subject having a left ventricular ejection fraction (LVEF) of less than 30%.

5 . The method according to claim 1 , wherein advanced ischemic cardiomyopathy is indicated by the subject having NTProBNP levels greater than 500 pg/ml.

6 . A method of treating a subject having advanced ischemic cardiomyopathy, the method comprising:
identifying a subject having an ischemic heart condition; determining the subject's end systolic volume; and administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 if the subject's end systolic volume is indicative of advanced ischemic cardiomyopathy.

7 . The method according to claim 6 , wherein the subject's end systolic volume is about 151 ml.

8 . The method of claim 1 or claim 6 , wherein the plasmid encoding SDF-1 comprises a polynucleotide having the sequence of SEQ ID NO:6.

9 . The method of claim 1 or claim 6 , wherein the amount of plasmid encoding SDF-1 administered to the subject is from about 25 mg to about 35 mg of said plasmid.

10 . The method of claim 9 , wherein the amount of plasmid encoding SDF-1 administered to the subject is about 30 mg of said plasmid.

11 . The method of claim 1 or claim 6 , wherein the plasmid encoding SDF-1 is administered via direct injection.

12 . The method of claim 1 or claim 6 , wherein the plasmid encoding SDF-1 is administered via endoventricular injection.

13 . The method of claim 1 or claim 6 , wherein the plasmid encoding SDF-1 is administered via a catheter.

14 . The method of claim 1 or claim 6 , wherein the plasmid encoding SDF-1 is administered via retrograde infusion.

15 . The method of claim 1 or claim 6 , further comprising evaluating the subject's cardiac output, biomarker expression, or both.

16 . The method of claim 15 , wherein evaluating the subject's cardiac output comprises evaluating the subject's cardiac volume.

17 . The method of claim 15 , wherein evaluating the subject's cardiac output comprises evaluating a six-minute walk distance.

18 . The method of claim 17 , wherein evaluating the subject's biomarker expression comprises evaluating a level of NTproBNP.

19 . The method of claim 1 or claim 6 , wherein the subject is human.

20 . The method of claim 1 or claim 6 , wherein the advanced ischemic cardiomyopathy is advanced heart failure.

Assignees

• Penn Marc S
• Pastore Joseph
• Miller Timothy J
• Juventas Therapeutics Inc
• Cleveland Clinic Found

Inventors

• Penn Marc S
• Aras Rahul
• Pastore Joseph
• Miller Timothy J

Classifications

• A61K48/005

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title

• A61K38/195 Primary

  Chemokines, e.g. RANTES · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title