The "EVERREST" Project

The EVERREST project is testing out a new treatment to improve the growth of babies with fetal growth restriction in the womb. An injection will be given into the two mother’s arteries which supply the womb with blood. This injection will contain a form of gene therapy to make the mother’s arteries produce more of a protein called VEGF. This protein will increase the blood supply to the womb and placenta and improve growth of the baby in the womb.

This would mean that affected babies could be delivered later and would weigh more, giving them a better chance of survival after birth and improving their outcome. What is most promising is that relatively small increases in growth of the baby and gestational age at delivery are associated with major improvements in survival and morbidity. For example, as each day of pregnancy advances between 24 and 27 weeks of gestation, there is a 2% improvement in survival after birth. Between 23 and 26 weeks of gestation, an increase in birthweight of 100g reduces the risk of dying by 40%.

The following flowchart describes the steps that will be undertaken during the project from start to finish. In October 2014, following completion of the Bioethical study, the EC confirmed that there are no fundamental ethical objections to the use of Maternal Growth Factor Therapy and the project could continue.

Bioethical Study

Using maternal growth factor therapy in pregnancy raises ethical questions. To address these a bioethicist will be carrying out research with patients and stakeholders into the ethical issues and public opinion around maternal growth factor therapy in pregnancy.
Leader: QMUL
Partners Involved: UCL, UKE, IDIBAPS, ULUND

Bioethical study confirms no ethical
objections to Maternal Growth Factor therapy. Project continues.

Preclinical Studies

Reproductive toxicology experiments will be carried out in a validated laboratory model to check for any safety issues, in particular what a toxic effect might look like and whether it crosses the placenta to the baby.
Leader: UCL
Partners Involved: FinVector, Magnus

Clinical Trial Design / Prospective Study

At four clinical centres, data on the outcome of pregnancies affected by severe early onset fetal growth restriction will be carefully collected into a prospective database so that it can be used to compare outcomes with treated pregnancies in the trial.
The clinical trial protocol will also be designed.
Leader: UCL
Partners Involved: UKE, IDIBAPS, ULUND, Magnus

Ethical and Regulatory Approval for the Clinical Trial

The Consortium will then apply for ethical and regulatory approval to do the trial at the four clinical centres.
Leader: UCL
Partners Involved: FinVector, QMUL, UEF, UKE, IDIBAPS, ULUND, Magnus

Women with pregnancies affected by severe early onset fetal growth restriction being managed in the four project centres will be given the opportunity to enter the Phase I/IIa study.
Leader: UCL
Partners Involved: FinVector, UKE, IDIBAPS, ULUND, Magnus

EVERREST Clinical Trial Begins