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

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.

Author information

1
Summa Cardiovascular Institute, Summa Health System, Skirball Laboratory for Cardiovascular Cellular Therapeutics, Department of Integrative Medical Sciences, Northeast Ohio Medical University, Akron, OH 44304, USA. mpenn2@neomed.edu

Abstract

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.

PMID:
23429605
DOI:
10.1161/CIRCRESAHA.111.300440
[Indexed for MEDLINE]
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