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Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth restriction

David, AL; (2017) Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth restriction. Placenta , 59 (S1) S44-S50. 10.1016/j.placenta.2017.09.011. Green open access

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Abstract

Intrauterine growth restriction (IUGR) is a serious pregnancy complication affecting approximately 8% of all pregnancies. The aetiology is believed to be insufficient maternal uteroplacental perfusion which prevents adequate nutrient and oxygen availability for the fetus. There is no treatment that can improve uteroplacental perfusion and thereby increase fetal growth in the uterus. Maternal uterine artery gene therapy presents a promising treatment strategy for IUGR, with the use of adenoviral vectors encoding for proteins such as Vascular Endothelial Growth Factor (VEGF) demonstrating improvements in fetal growth and neonatal outcome in preclinical studies. Mechanistically, maternal VEGF gene therapy delivered to the uterine arteries increases uterine blood flow and enhances vascular relaxation short term, while reducing vascular contractility long term. It also leads to vascular remodeling with increased endothelial cell proliferation in the perivascular adventitia of uterine arteries. Safety assessments suggest no vector spread to the fetus and no adverse risk to the mother or fetus; a clinical trial is in development. This article assesses research into VEGF maternal uterine artery directed gene therapy for IUGR, investigating the use of transgenes and vectors, their route of administration in obstetrics, and the steps that will be needed to take this treatment modality into the clinic.

Type: Article
Title: Maternal uterine artery VEGF gene therapy for treatment of intrauterine growth restriction
Location: Orlando, FL
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.placenta.2017.09.011
Publisher version: https://doi.org/10.1016/j.placenta.2017.09.011
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Intrauterine growth restriction, Vascular endothelial growth factor, Uterine blood flow, Gene therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10044770
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