What did the project achieve?
“When we first started this project, treating craniosynostosis seemed a long way off – but we’ve now made real progress towards our goal of developing a new drug treatment that can help reduce the impact of this disease on children’s lives,” says Dr Dagan Jenkins of the UCL Great Ormond Street Institute of Child Health. “We hope the approach will ultimately help reduce the need for repeat surgery and improve the appearance of the head.”
Around 350 children are born with craniosynostosis every year in the UK. Their bones in the skull fuse together too early, causing an abnormally shaped head and leaving no room for their brain to grow. Surgeons try to correct this by creating new gaps, but unfortunately, these can join back together and children will often need to undergo follow-up operations.
Dr Jenkins’ team has investigated whether applying an existing drug to the site of surgery can help prevent the skull bones from re-fusing. Their first task involved developing a new material that can be applied to the surgical wound like a plaster, which has been shown to deliver the drug at suitable concentrations over a period of three months only to where it’s needed – avoiding the risk of potential side effects.
“This is an important step as the drug will need to exert long-lasting effects at the site of surgery to work,” says Dr Jenkins. “We’ve also demonstrated that applying the drug-soaked material can prevent craniosynostosis on skull tissue from a laboratory model grown in a dish.”
In further laboratory experiments to investigate whether the drug also works on human cells, the researchers have tested the drug-soaked material on cells derived from small pieces of tissue collected from 21 children undergoing surgery for craniosynostosis.
“Remarkably, we found it was possible to encourage these cells to form new bone – mirroring the process of skull re-fusion that happens after surgery in these children,” says Dr Jenkins. “We showed that we could slow down this process using the drug-soaked material.”
The team has also developed another laboratory model for craniosynostosis, showing that small gaps created in a skull bone through surgery can repair themselves in three weeks.
“We’re now planning to test our new drug treatment in this model to find out if it can help prevent new bone from forming at the site of surgery over a longer period, of months,” says Dr Jenkins. “If these laboratory experiments are successful, we will then be able to test the drug in a clinical trial – which is the last piece of the jigsaw.”
Using the latest gene sequencing technologies, the team has also identified new molecules that may play an important role during the process of skull bone fusion – identifying potential new targets for the development of future treatments.
This research was completed on
About 350 children are born with craniosynostosis every year in the UK.1,2 In children with this condition, the bones in the skull fuse together too early, causing an abnormally shaped head and leaving no room for the brain to grow. Surgeons try to correct this by creating new gaps, but unfortunately these can join back together and children will often need follow-up operations. Dr Dagan Jenkins at the UCL Great Ormond Street Institute of Child Health aims to find out whether a drug can help improve treatment for children by reducing the need for repeat surgery and improving the appearance of the head.
How are children’s lives affected now?
Children with craniosynostosis can experience persistent headaches, learning disabilities and vision and hearing problems, which are caused by increased pressure within their skull.
To prevent these symptoms, babies often need surgery to correct their abnormal head shape and make room for their brains to grow. But unfortunately, for many children one operation is not enough.
“While current surgical procedures are very effective, they can be complicated and require many hours under general anaesthetic – this is an issue, especially for young babies who may have other medical problems as well,” says Dr Jenkins. “Less invasive procedures have been developed, but these are not currently as effective – and there is also a risk that the gaps may join back together and further surgery will be required.”
“Coping with the news that your baby has such a serious condition is difficult enough, so we really want to improve current treatments so that they are both more effective and reduce the impact on these young lives,” says Dr Jenkins.
How could this research help?
“This is a completely unique study. We hope that applying a drug to the site of surgery will improve the effectiveness of the less invasive procedures without the need for follow-up operations – meaning that affected babies can look forward to a more typical childhood,” says Dr Jenkins.
The team have identified a drug – that is already approved to treat very young children with other conditions – which could also be helpful for treating craniosynostosis by stopping the skull bones from re-fusing.
They now plan to test this drug in a series of experiments in the laboratory, using a new technique that they hope can deliver it specifically to the gaps that the surgeon creates in the skull. “By applying the drug only to where it’s needed, we hope this will greatly reduce the risk of side effects,” says Dr Jenkins.
The researchers hope that the results will lay the foundations to support a clinical trial in patients in the future.
- NHS Choices website http://www.nhs.uk/Conditions/Craniosynostosis/Pages/Introduction.aspx [accessed 21/08/2017]
- Wilkie AO et al. Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis. Pediatrics 2010 126(2):e391-400
|Dr Dagan Jenkins, BSc PhD
|Mr David JohnsonProfessor T R Arnett, BSc PhDDr Steve R F Twigg, BSc DPhilProfessor Andrew O M Wilkie, MA BM BCh DM DCH FRCP FESB FMedSci FRSDr Erwin Pauws, BSc PhD
|UCL Great Ormond Street Institute of Child Health, University College London
|Project Location Other
|Oxford Craniofacial Unit, John Radcliffe Hospital, Oxford Department of Cell and Developmental Biology, University College LondonClinical Genetics Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OxfordDevelopmental Biology and Cancer Programme, UCL Great Ormond Institute of Child Health, London
|24 July 2017
|Project start date
|16 October 2017
|Project end date
|15 October 2019