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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
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| Zeitschriftentitel: | Circulation Research |
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| Personen und Körperschaften: | , , , , , , , , , |
| In: | Circulation Research, 112, 2013, 5, S. 816-825 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
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| Schlagwörter: |
| Zusammenfassung: | <jats:sec> <jats:title> <jats:underline>Rationale:</jats:underline> </jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Objective:</jats:underline> </jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Methods and Results:</jats:underline> </jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Conclusions:</jats:underline> </jats:title> <jats:p>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.</jats:p> </jats:sec> |
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| Umfang: | 816-825 |
| ISSN: |
0009-7330
1524-4571 |
| DOI: | 10.1161/circresaha.111.300440 |