preventing infection-related preterm birth and associated brain injury

INSTITUTION: King’s College London
RESEARCHERS: Professor D Peebles, Dr S Waddington, Dr N Suff, Dr A Rahim

Children who survive premature birth can experience lifelong conditions such as cerebral palsy, learning difficulties, blindness and hearing loss.

In this project, funded jointly by Borne and Action Medical Research, Professor Donald Peebles at University College London is developing an innovative new gene therapy that could help prevent preterm birth and protect the baby’s brain.

about the research

Evidence suggests that bacteria can pass into the womb and trigger inflammation, which can cause early labour and damage the baby’s developing brain.

Babies born early can suffer brain damage from the premature birth and from infection-related brain injury. Anti-bacterial molecules produced in the cervix help to stop bacteria from getting through. The team is developing a new gene therapy that is designed to boost these natural defences, helping to protect the womb from infection.

Professor Peebles and his team are using a laboratory model (mouse) to investigate whether, by preventing bacteria from travelling from the vagina into the uterus during pregnancy, it is possible to reduce fetal inflammation and brain damage. The plan is to use gene therapy (an adeno-associated viral (AAV) vector-based delivery system) to boost levels of natural antimicrobial peptide (AMP), called human beta-defensin 3 (HBD3), at the cervix.

“We are aiming to develop a new treatment that can help prevent bacteria getting into the womb. Our hope is it could both reduce the numbers of premature births, as well as reduce the risk of brain damage and its long-lasting impact on children’s lives.”

– Professor Donald Peebles

UPDATES & IMPACT

Borne and Action Medical Research funding is enabling the team to investigate the extent of brain damage in the laboratory model. They have found evidence that multiple protein and gene markers of inflammation are increased in the brains soon after infection. Further testing will take place to determine the extent of brain damage at different times after birth.

To determine the effect of gene therapy on survival as well as brain damage following bacterial infection, the gene therapy has now been produced to investigate its effect in the laboratory model. In the next step, the researchers aim to compare the effects of the gene therapy with another antimicrobial protein, either alone or in combination, on survival and brain damage following bacterial infection.

Ultimately, this work could lead to the first-in-human trial of this kind and the development of a much-needed new treatment to prevent preterm birth. In addition, if the treatment is shown to prevent infection-related brain injury, this would further support the long-term aim of reducing the number of babies born with permanent brain injury as a result of preterm delivery.

Another outcome from the project so far includes publication of an abstract at international meeting.

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