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Direct intramyocard...
Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
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Anttila, V. (author)
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Saraste, A. (author)
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Knuuti, J. (author)
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Hedman, M. (author)
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Jaakkola, P. (author)
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Laugwitz, K. L. (author)
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Krane, M. (author)
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- Jeppsson, Anders, 1960 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Sillanmäki, S. (author)
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Rosenmeier, J. (author)
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Zingmark, P. (author)
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Rudvik, A. (author)
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Garkaviy, P. (author)
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Watson, C. (author)
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Pangalos, M. N. (author)
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- Chien, K. R. (author)
- Karolinska Institutet
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Fritsche-Danielson, R. (author)
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Collén, A. (author)
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- Gan, Li-Ming, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- CABG
- cardiac
- clinical trial
- EPICCURE
- LVEF
- mRNA
- phase 2a
- regeneration
- safety
- therapeutic mRNA
- tolerability
- VEGF-A
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Anttila, V.
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Saraste, A.
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Knuuti, J.
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Hedman, M.
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Jaakkola, P.
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Laugwitz, K. L.
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show more...
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Krane, M.
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Jeppsson, Anders ...
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Sillanmäki, S.
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Rosenmeier, J.
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Zingmark, P.
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Rudvik, A.
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Garkaviy, P.
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Watson, C.
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Pangalos, M. N.
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Chien, K. R.
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Fritsche-Daniels ...
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Collén, A.
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Gan, Li-Ming, 19 ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Molecular Therap ...
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Molecular therap ...
- By the university
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University of Gothenburg
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Karolinska Institutet