| Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. | |
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MedLine Citation:
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PMID: 18514926 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Heart failure (HF) remains a major cause of morbidity and mortality in North America. With an aging population and an unmet clinical need by current pharmacologic and device-related therapeutic strategies, novel treatment options for HF are being explored. One such promising strategy is gene therapy to target underlying molecular anomalies in the dysfunctional cardiomyocyte. Prior animal and human studies have documented decreased expression of SERCA2a, a major cardiac calcium cycling protein, as a major defect found in HF. METHODS AND RESULTS: We hypothesize that increasing the activity of SERCA2a in patients with moderate to severe HF will improve their cardiac function, disease status, and quality of life. Gene transfer of SERCA2a will be performed via an adeno-associated viral (AAV) vector, derived from a nonpathogenic virus with long-term transgene expression as well as a clinically established favorable safety profile. CONCLUSIONS: We describe the design of a phase 1 clinical trial of antegrade epicardial coronary artery infusion (AECAI) administration of AAVI/SERCA2a (MYDICAR) to subjects with HF divided into 2 stages: in Stage 1, subjects will be assigned open-label MYDICAR in one of up to 4 sequential dose escalation cohorts; in Stage 2, subjects will be randomized in parallel to 2 or 3 doses of MYDICAR or placebo in a double-blinded manner. |
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Authors:
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Roger J Hajjar; Krisztina Zsebo; Lawrence Deckelbaum; Craig Thompson; Jeff Rudy; Alex Yaroshinsky; Hung Ly; Yoshiaki Kawase; Kim Wagner; Kenneth Borow; Brian Jaski; Barry London; Barry Greenberg; Daniel F Pauly; Richard Patten; Randall Starling; Donna Mancini; Mariell Jessup |
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Publication Detail:
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Type: Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural Date: 2008-05-27 |
Journal Detail:
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Title: Journal of cardiac failure Volume: 14 ISSN: 1532-8414 ISO Abbreviation: J. Card. Fail. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-02 Completed Date: 2008-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9442138 Medline TA: J Card Fail Country: United States |
Other Details:
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Languages: eng Pagination: 355-67 Citation Subset: IM |
Affiliation:
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Mount Sinai School of Medicine, New York, New York 10029, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adrenergic beta-Antagonists / therapeutic use Adult Aged Angiotensin-Converting Enzyme Inhibitors / therapeutic use Combined Modality Therapy Coronary Vessels Dependovirus* Diuretics / therapeutic use Double-Blind Method Drug Therapy, Combination Female Gene Therapy* Genetic Vectors* Green Fluorescent Proteins Heart Failure / drug therapy, enzymology, genetics, therapy* Humans Male Middle Aged Receptors, Angiotensin / agonists Sarcoplasmic Reticulum Calcium-Transporting ATPases / administration & dosage, genetics*, metabolism Transduction, Genetic / methods* Transgenes |
| Grant Support | |
ID/Acronym/Agency:
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HL071763/HL/NHLBI NIH HHS; HL080498/HL/NHLBI NIH HHS; HL083156/HL/NHLBI NIH HHS; R01 HL078691/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Diuretics; 0/Receptors, Angiotensin; 147336-22-9/Green Fluorescent Proteins; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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