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What did the project achieve?
"Our research has shown that a commonly used diabetes medicine is effective at protecting the brain from damage at birth in the laboratory – either alone or in combination with cooling therapy, which is now routine in the UK," says Professor Ahad Rahim of University College London. "These results are exciting – since this drug is already used in the clinic so it could be easier and faster to potentially use it to treat newborn babies from serious brain injury – helping to save lives and prevent long-term disabilities."
Estimates suggest over 2,000 babies in the UK develop a life-threatening brain condition called neonatal encephalopathy (NE) each year.1,2 Often caused by a shortage of oxygen to the brain around the time of birth, NE puts babies’ lives in immediate danger. Cooling a baby for three days after birth gives them a better chance of surviving and escaping lifelong disabilities. But sadly, this revolutionary treatment doesn’t save or protect the brain of all babies.
This project investigated whether a drug that is already used to treat diabetes could also be used in the future to protect a baby’s brain from damage due to NE. Previous research has shown that this medicine can protect the brain from damage in various other conditions – and it has been successfully used in clinical trials for treating Parkinson’s disease.
“Our results show that exendin-4 prevents the loss of important brain cells called neurons, in the laboratory – and, at the same time, it also reduces inflammation and other processes known to be harmful,” says Professor Rahim. “In addition, we found that combining this existing drug with cooling therapy can further boost its effectiveness, which is also very encouraging.”
Due to these promising results, the researchers are currently engaging with leading clinicians in UK and Europe to explore how to take forward this drug into a clinical trial to test its safety and effectiveness at protecting the brains of newborn babies affected with NE.
This research was completed on
Latest data suggests over 1,200 babies develop a life-threatening brain condition called neonatal encephalopathy (NE) each year in the UK.1,2 Often caused by a shortage of oxygen to the brain around the time of birth, NE puts babies’ lives in immediate danger. Those who survive can be left with lifelong disabilities. Cooling a baby’s temperature down for three days after birth gives them a better chance of surviving and escaping disability. Sadly though, this doesn’t save all babies. Dr Ahad Rahim, of University College London, is investigating whether a commonly used diabetes medicine might improve babies’ chances.
How are babies’ lives affected now?
Estimates suggest around 700,000 babies worldwide die or develop disabilities each year because of NE, a serious condition which can leave the brain permanently damaged.1
NE affects newborn babies in the first hours or days of life. “The severity of NE varies considerably,” says Dr Rahim. “Sadly, around one in five babies with NE in the UK dies.3 Many others develop lifelong problems such as cerebral palsy and learning difficulties. The emotional and financial costs of caring for these children can be enormous.”
Action Medical Research part-funded previous research that led to the important finding that cooling a baby’s temperature down slightly for three days after birth improves their chances of surviving and escaping disability. This revolutionary cooling therapy is now routine in the UK. Unfortunately though it doesn’t save every baby; some babies with NE still die or develop disabilities.3 “There is an overwhelming need for further improvements in the treatment of NE,” says Dr Rahim.
How could this research help?
The researchers have made an exciting discovery that a diabetes medicine called exendin-4 might benefit babies with NE. They are investigating this possibility further in the laboratory.
Exendin-4 is thought to have protective effects on the brain. Clinical trials are already underway to find out whether it benefits people with two other conditions that involve changes in the brain: Alzheimer’s disease and Parkinson’s disease.
In this project, the researchers are investigating what dose of exendin-4 babies with NE might need by first testing different dose regimens in a rodent model that mimics NE in babies. They also aim to find out more about the medicine’s safety profile, how it works to protect the brain and the possible benefits it might bring whether used alone or in combination with cooling therapy.
“Further research will be needed,” says Dr Rahim, “but we hope that exendin-4 will one day prove to be a much-needed new treatment that improves the chances of babies with NE.”
References
1. Lee ACC et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatric Research 2013; 74: 50-72.
2. Office for National Statistics. Vital Statistics: Population and Health Reference Tables. http://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationestimates/datasets/vitalstatisticspopulationandhealthreferencetables Website accessed 18 September 2016.
3. Azzopardi D et al. Implementation and Conduct of Therapeutic Hypothermia for Perinatal Asphyxial Encephalopathy in the UK – Analysis of National Data. PLOS One 2012; 7(6): e38504.
| Project Leader | Dr Ahad A Rahim BSc PhD |
| Project Team | Professor Henrik Hagberg MD PhDDr Claire Thornton BSc MSc PhDDr Eridan Rocha-Ferreira BSc PhD |
| Project Location | Department of Pharmacology, School of Pharmacy, University College London |
| Project Location Other | Perinatal Brain Injury Group, Division of Imaging Sciences and Biomedical Engineering, St Thomas' Hospital, King’s College LondonDepartment of Fetal and Maternal Medicine, Institute for Women's Health, University College London |
| Project duration | 3 years |
| Date awarded | 21 July 2016 |
| Project start date | 1 May 2017 |
| Project end date | 30 Jan 2021 |
| Grant amount | £193,585 |
| Grant code | GN2485 |
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