Therapy for placental insufficiency leading to fetal growth restriction
Placental insufficiency leading to FGR is an incurable condition where fetal growth in the womb is unnaturally slow. In placental insufficiency there is reduced blood flow to the womb. This places babies resulting from such pregnancies at high risk of long-term health problems. Improving blood flow to the womb would significantly improve the outcome for such babies. Women with normal pregnancies have appropriate levels of vascular endothelial growth factor (VEGF) levels in their blood, resulting in healthy blood flow to the womb. VEGF is a protein secreted by the placenta and women with FGR could benefit if the local VEGF levels in the blood supply to the womb are enhanced via techniques such as gene therapy. Recently, use of growth factor therapy in animals dramatically enhanced fetal growth through dilating the vessels supplying the womb and by providing new blood vessel formation that increased blood flow to the womb. The EVERREST(opens in new window) consortium will demonstrate the safety and efficacy of this maternal growth factor therapy via pre-clinical studies followed by clinical trials. Initially, EVERREST members investigated the social acceptability and ethical issues involved in using gene medicine in pregnancy. Results revealed a mostly favourable mindset towards pregnant women participating in such clinical trials. Pre-clinical studies are being carried out to demonstrate the safety of maternal growth factor therapy. Tissue from human placentas exposed in the laboratory to high doses of the gene medicine did not show any damage. Laboratory testing is ongoing to determine if gene medicine crosses the placenta, though initial animal testing did not demonstrate this. In addition, comprehensive reproductive toxicology studies will be carried out on pregnant animals to study the effects of high and low doses of the gene medicine. Women with severe early-onset FGR are being recruited at the four study sites for an observational study aiming to collect comprehensive data about untreated affected pregnancies. EVERREST has also established a biobank of samples from women and babies with FGR. The clinical trial protocol for phase I/IIa study has been drafted. Positive clinical trial outcomes will advance clinical research in obstetric therapy. This should facilitate faster commercialisation of gene therapy for FGR, hopefully within the next 10 to 15 years.
