An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure

Circ Res. 2013 Mar 1;112(5):816-25. doi: 10.1161/CIRCRESAHA.111.300440. Epub 2013 Feb 21.


Rationale: Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1.

Objective: We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters.

Methods and results: Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3-61 minutes]; 30 mg: 31 minutes [22-74 minutes]) and quality of life (15 mg: -16 points [+1 to -32 points]; 30 mg: -24 points [+17 to -38 points]) over baseline. At 12 months, improvements in symptoms were maintained.

Conclusions: These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Echocardiography
  • Exercise Tolerance
  • Female
  • Follow-Up Studies
  • Genetic Therapy / adverse effects*
  • Genetic Therapy / methods*
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Heart Failure / therapy*
  • Humans
  • Male
  • Middle Aged
  • Myocardium / metabolism
  • Myocardium / pathology
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Plasmids*
  • Positron-Emission Tomography
  • Quality of Life
  • Treatment Outcome


  • Chemokine CXCL12
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain