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The Evidence So Far

Vascular Endothelial Growth Factor (VEGF) is a protein which causes blood vessels to dilate and new blood vessels to be formed. In normal pregnancies the uterine arteries, which supply the womb with blood, relax and dilate so blood can flow easily to the placenta. One of the things that causes this is VEGF produced by the placenta and released into the mother’s blood. Studies have shown that in Fetal Growth Restriction (FGR) there is reduced blood flow to the womb (1) and there are also lower levels of VEGF in the maternal blood (2, 3).

Studies in pregnant women have been performed over the last 6 years by researchers at UCL Institute for Women’s Health and Cardiovascular Medicine, and the Rowett Institute of Nutrition and Health at University of Aberdeen, together with Ark Therapeutics. They identified that maternal blood flow to the placenta could be increased both short term and long term in normal pregnancies by delivering an adenoviral vector gene medicine containing the Vascular Endothelial Growth Factor (VEGF) to the uterine arteries (4, 5). There was evidence of new vessel formation in the uterine arteries in association with the VEGF protein, and the uterine arteries were more relaxed and less constricted. There was increased levels in the uterine arteries of a protein called nitric oxide synthase, which is fundamentally important in maintaining blood flow in arteries (4, 5).

In growth restricted sheep and guinea pig pregnancies the adenoviral vector VEGF gene medicine safely increased fetal growth and birthweight (6, 7). So far the experiments have shown no harm to the mother, fetus or neonate from the therapy and have found no evidence of it crossing the placenta (4, 5).

References

  1. Konje JC, Howarth ES, Kaufmann P, Taylor DJ. Longitudinal quantification of uterine artery blood volume flow changes during gestation in pregnancies complicated by intrauterine growth restriction. British Journal of Obstetrics and Gynaecology 2003;110:301-5. PMID:12628272

  2. Savvidou MD, Yu CK, Harland LC, Hingorani AD, Nicolaides KH. Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular endothelial growth factor in women with abnormal uterine artery Doppler and in those with fetal growth restriction. Am J Obstet Gynecol 2006 Dec;195(6):1668-73. PMID:16643817

  3. Bersinger NA, Odegard RA. Serum levels of macrophage colony stimulating, vascular endothelial, and placenta growth factor in relation to later clinical onset of pre-eclampsia and a small-for-gestational age birth. Am J Reprod Immunol 2005 Aug;54(2):77-83. PMID:16105099

  4. David AL, Torondel B, Zachary I, Wigley V, Abi-Nader K, Mehta V, et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Therapy 2008;15:1344-50. PMID:18563186

  5. Mehta V, Abi-Nader KN, Peebles DM, Benjamin E, Wigley V, Torondel B, Filippi E, Shaw SW, Boyd M, Martin J, Zachary I, David AL. Long- term increase in uterine blood flow is achieved by local overexpression of VEGF-A165 in the uterine arteries of pregnant sheep. Gene Therapy. 2012 Sep;19(9):925-35. doi: 10.1038/gt.2011.158. Epub 2011 Oct 20. PMID:22011641

  6. Carr DJ, Wallace JM, Aitken RP, Milne JS, Mehta V, Martin JF, Zachary IC, Peebles DM, David AL. Uteroplacental adenovirus vascular endothelial growth factor gene therapy increases fetal growth velocity in growth-restricted sheep pregnancies. Hum Gene Ther. 2014 Apr;25(4):375-84. (link: http://www.ncbi.nlm.nih.gov/pubmed/22648778)

  7. Mehta V, Boyd M, Martin J, Zachary I, Peebles DM, David AL. Local administration of Ad.VEGF-A165 to the utero-placental circulation enhances fetal growth and reduces brain sparing in an FGR model of guinea pig pregnancy. Reproductive Sciences 2012;19(3).