Preventing infections that cause preterm birth
Research institutes:
Department of Maternal
and Fetal Medicine,
Institute for Women’s Health,
University College LondonProject dates:
Grant Awarded: 21 Nov 2017
Funding awarded:
Grant Amount (Borne’s share): £70,974.50
Total Award: £141,949
Infections in the womb are one of the most common triggers for preterm birth, and can cause long-term brain damage to the baby. In this project, Prof Donald Peebles and his team tested a new therapy to boost the natural defences that prevent bacterial infections in the womb. This could lead to a new treatment that prevents babies from being born too soon.
The challenge
As many as 4 in 10 cases of preterm birth are caused by infections from bacteria travelling up from the vagina, through the cervix, and into the womb. What’s more, we know that infections can cause additional problems to the brains of unborn babies, including cerebral palsy, learning difficulties, and sight or hearing loss.
We need to find ways to prevent infections from causing premature births and long-term brain damage to babies, so that we can help more babies survive and thrive.
The project
The human cervix produces natural antibacterial proteins which can prevent some infections from travelling from the vagina into the womb. Prof Donald Peebles and his team are trying to develop a gene therapy to boost the production of these antibacterial proteins by the cervix. Their hope is that this gene therapy will reduce preterm birth caused by infection, and the long-term health problems this can cause.
In this project, which ended in September 2022, Prof Peebles’s team first used pregnant mice to investigate the effects of different bacteria on the brains of unborn mice pups. They confirmed that a strain of E. coli which causes meningitis does cause premature birth, and reduces the chances survival of the mice pups. Less harmful E. coli strains did not have this effect.
This meningitis-causing E. coli strain also caused inflammation in the brain of the mice pups, which lasted longer than other less harmful strains of bacteria.
Prof Peebles and his team then tested their new ‘gene therapy’ which causes the cervix to produce an antibacterial protein called HBD3. The team found their gene therapy to boost production of HBD3 in the cervix did not prevent premature birth in the pregnant mice, when exposed to the harmful E. coli strain.
However, the therapy did increase the number of pups born alive, and improved long-term survival of these pups. The treatment also reduced the signs of inflammation in the brain of these pups.
They also tested a gene therapy for a different antibacterial protein, which had similar effects.
What difference will this project make?
Infections are a common cause of preterm birth, and the inflammation they cause can damage the brain of unborn children causing long-term disability or even death. So, we must find ways to prevent infections in the womb from causing harm to babies.
Prof Peebles and his team have developed a gene therapy to boost the cervix’s natural antibacterial defences. Based on the results of their study, they believe that the HBD3 gene therapy warrants further investigation.
They have since received funding from the charity Wellbeing of Women to continue and build on this work, as well as a further jointly-funded grant from Borne and Action Medical Research. After this work is complete, they hope to start the process of developing a first-in-human clinical trial of their treatment.
If successful, this work could eventually lead to a new treatment to stop babies from being born too soon, and to reduce the long-term health impact of premature birth.
Preterm birth is a significant global health issue, accounting for approximately 11% of births worldwide and is the leading cause of morbidity and mortality in babies. Currently, treatments are limited. Funding from Borne and Action Medical Research has been fundamental in supporting our research to develop a novel therapy to preventatively treat mothers at high risk of preterm labour in order to improve the health of premature babies.
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This project is jointly funded by Borne and Action Medical Research.
