In the EU alone, around 11,000 babies per year are affected as a result of placental insufficiency leading to foetal growth restriction (FGR) in the womb. Researchers are investigating the effectiveness of a promising maternal growth factor therapy during pregnancy via preclinical and then human clinical trials.
Placental insufficiency leading to FGR is an incurable condition where fetal growth in the womb is unnaturally slow or even stops altogether. In placental insufficiency there is reduced blood flow to the womb. This places babies resulting from such pregnancies at high risk of blindness, cerebral palsy, breathing difficulties, and long-term, adults suffer with cardiovascular and metabolic disorders such as diabetes. Placental insufficiency is a major cause of stillbirth and neonatal death. Improving blood flow to the womb might 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 might benefit if the local VEGF levels in the blood supply to the womb were enhanced via techniques such as gene therapy.
Research, using pregnant sheep and guinea pigs at the Royal Veterinary College, is developing a treatment to improve foetal growth before birth. Recently, they showed that use of VEGF growth factor therapy in pregnant sheep with placental insufficiency dramatically enhanced foetal growth through dilating the vessels supplying the womb and by providing new blood vessel formation. This increases blood flow to the womb providing oxygen and nutrients for foetal growth. Pregnancy in guinea pigs is more similar to humans, in terms of hormonal changes in the mother, the structure of the placenta and the level of maturity of the newborn. Thus guinea pigs are an excellent model in which to investigate the effectiveness and long-term safety of foetal growth therapies. Since pregnancy in the guinea pig is relatively long compared to other rodents, gene therapy can be administered in mid-pregnancy and the effects measured just before birth.
To date, these studies have demonstrated increased total body weight and brain weight following gene therapy, in guinea pig foetuses that were growth restricted by limiting maternal calorie intake. Ongoing analyses are being conducted in the pups exposed to gene therapy to find out whether there are improvements in their postnatal growth, metabolism and cardiovascular function.
The EVERREST consortium which is funded by the European Union, will demonstrate the safety and efficacy of this maternal growth factor therapy via clinical trials. EVERREST members recently 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. For further information see www.everrest-fp7.eu Twitter @FP7EVERREST.