Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting

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

Saraste, A. (author)
Knuuti, J. (author)
Hedman, M. (author)
Jaakkola, P. (author)
Laugwitz, K. L. (author)
Krane, M. (author)
Jeppsson, Anders,1960Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xjepan (author)
Sillanmäki, S. (author)
Rosenmeier, J. (author)
Zingmark, P. (author)
Rudvik, A. (author)
Garkaviy, P. (author)
Watson, C. (author)
Pangalos, M. N. (author)
Chien, K. R.Karolinska Institutet (author)
Fritsche-Danielson, R. (author)
Collén, A. (author)
Gan, Li-Ming,1969Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xganli (author)
Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)

In:Molecular Therapy: Elsevier BV31:3, s. 866-8741525-0016
In:Molecular therapy : the journal of the American Society of Gene Therapy: Elsevier BV31:3, s. 866-8741525-0024

About the subject

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.