Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
: Anttila Vesa, Saraste Antti, Knuuti Juhani, Hedman Marja, Jaakkola Pekka, Laugwitz Karl-Ludwig, Krane Markus, Jeppsson Anders, Sillanmäki Saara, Rosenmeier Jaya, Zingmark Pernilla, Rudvik Anna, Garkaviy Pavlo, Watson Christina, Pangalos Menelas N., Chien Kenneth R., Fritsche-Danielson Regina, Collén Anna, Gan Li-Ming
: 2023
: Molecular Therapy
: Molecular therapy : the journal of the American Society of Gene Therapy
: Mol Ther
: 31
: 3
: 866
: 874
: 1525-0016
: 1525-0024
DOI: https://doi.org/10.1016/j.ymthe.2022.11.017
: https://research.utu.fi/converis/portal/detail/Publication/178102444
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.
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