17 January 2013
UCL researchers in a successful
academic-industrial collaboration have been awarded an EU
Framework Programme 7 Grant of almost €6 million to develop a therapy for foetal growth restriction.
The funding has been
awarded to the EVERREST* consortium of seven leading EU higher education institutions, led
by UCL. The main industrial collaborator engaged in the research is Ark
Therapeutics Group plc, London, UK, a contract development and manufacturing
organisation with specialist expertise and facilities for the development of
viral based products.
The consortium is developing a
therapy for foetal growth restriction, a major problem of pregnancy affecting up
to eight per cent of all pregnancies. The condition is severe in approximately 1 in 500
foetuses and affected foetuses are extremely small, usually less than 500g.
Babies born from growth restricted pregnancies are not only at increased risk
of perinatal death and complications such as cerebral palsy, but there are long
term consequences for their health which include diabetes and cardiovascular
The recent improvements in the postnatal care of premature growth
restricted babies means that more of them survive delivery, but at great cost. Inadequate uterine blood flow, termed ‘utero-placental
insufficiency’, is the underlying abnormality in many cases.
Currently there is no
Once severe early onset foetal growth restriction is
identified in mid pregnancy, couples currently face a stark choice between
delivering their baby very prematurely in the knowledge that they might die in
the neonatal intensive care unit, or allowing the pregnancy to continue with
the strong likelihood that the baby will die in the womb.
If successful, this would be the first evidence based therapy for fetal growth restriction and could save thousands of lives.
Dr Anna David, UCL Institute for Women's Health
Studies performed over the
last six years by researchers at the UCL Institute for Women’s Health and UCL
Department of Cardiovascular Medicine, with Ark Therapeutics, identified that
maternal blood flow to the placenta could be increased in normal pregnancies by
delivering a gene medicine containing the Vascular Endothelial Growth Factor
(VEGF) to the uterine arteries. In growth restricted pregnancies the gene
medicine safely increased foetal growth and birthweight.
What is most promising is
that relatively small increases in foetal growth 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 two per cent
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 per cent.
The new grant supports the EVERREST consortium’s
involvement in a six year research programme that will culminate in a
first-in-woman phase I/IIa safety/efficacy trial. The final pre-clinical
toxicology studies will be concluded by UCL and University of East Finland.
A leading bioethicist from Queen Mary
University of London will engage with stakeholder groups and patients affected
by foetal growth restriction to evaluate the ethical and social acceptability of
the proposed EVERREST trial.
For the trial, the consortium includes some of
the leading foetal medicine centres and academic health science centres in
Sweden (Lund University), Germany (University Medical Center
Hamburg-Eppendorf), Spain (Hospital Clinic Barcelona and IDIBAPS) and the UK
(UCL and UCLH) with strong backgrounds in the management of pregnancies
affected by severe early onset foetal growth restriction.
Women from these centres who present with an
affected pregnancy in mid-gestation will be invited to participate in the trial,
and the safety and efficacy of the intervention will be studied. The consortium
will be managed by Euram, a leading UK based research application and
Dr Anna David, Reader/Associate Professor at
UCL Institute for Women’s Health and the coordinator of the EVERREST consortium
said: “This award will enable the development of a highly innovative new
therapy in the field of obstetrics, a specialty in which there is currently a
lack of investment in new treatments. If successful, this would be the first
evidence based therapy for foetal growth restriction and could save thousands of
Foetal growth restriction
affects approximately 60,000 babies per year in Europe and the USA. Many of
these premature, very small babies stay in hospital for months after birth,
which is stressful for parents and very costly for the NHS (neonatal intensive
care costs approximately £1,000 per day). Potential benefits from the research could
include reduced stillbirths and neonatal deaths, and improved outcome in
pregnancies affected by severe early onset foetal growth restriction.
project is partially funded by the European Commission under the 7th Framework
Dr David is
currently funded by the National Institute for Health Research (NIHR)
Biomedical Research Centre at UCLH/UCL.
stands for: Does
vascular endothelial growth factor gene therapy safely
improve outcome in severe early-onset
foetal growth restriction?
Image caption: A baby with foetal growth restriction (credit: The Times, all rights reserved).
Media contact: David Weston
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