What did the project achieve?
“This project has helped improve our understanding of the biology of NKH and develop and test new treatments in the laboratory,” says Professor Nicholas Greene of the UCL Great Ormond Street Institute of Child Health. “Encouragingly, our preliminary results suggest that gene therapy could have the potential to treat children with this devastating illness in the future.”
Babies with non-ketotic hypergylcinemia (NKH) will usually become seriously ill within the first few days of life. Children who survive will go on to have severe problems including epilepsy, profound learning and physical disabilities. Sadly, there is no cure – and so there is an urgent need for new treatments.
The team previously generated a laboratory model with a faulty version of a gene that causes NKH, which is enabling them to better study the disease and develop and test new treatments.
“We have used our model to monitor electrical activity in the brain to look for signs of epilepsy, which will enable us to evaluate the effectiveness of potential new treatments in the future,” says Professor Greene. “We also used very sensitive tests to detect biochemical changes in the body that are caused by the faulty gene – and devised simple treatments to correct some of these changes.”
To achieve a more effective long-term treatment for NKH, the team is aiming to develop a gene therapy, which involves putting a healthy copy of the affected gene into patient cells to replace their faulty version.
“Our initial experiments indicate that using gene therapy could be an effective way to treat the disease,” says Professor Greene. “We have since generated the necessary tools and tested ways to get the healthy gene into cells – and we are now investigating the effectiveness of using this approach in the laboratory.”
This research was completed on
Children with a rare metabolic disease called non-ketotic hyperglycinemia (NKH) may one day benefit from research by Professor Nicholas Greene of University College London’s Institute of Child Health. Children with this devastating condition normally become ill soon after birth. Sadly, some lose their lives while just babies, some others during childhood. Professor Greene is investigating the disease processes that cause children’s symptoms, assessing the benefits of existing treatments and searching for new therapies. Although his work is still in the laboratory stages, Professor Greene hopes to develop treatments that one day reduce children’s suffering and perhaps even save their lives.
Action Medical Research and Great Ormond Street Children's Charity are jointly funding this research.
How are children’s lives affected now?
“NKH is a disease that affects around one in every 60,000 babies,” says Professor Greene.1,2 “Most become seriously ill during the first few days of life. They become floppy, lethargic and need help with their breathing. They can also have seizures.”
“Babies who survive can go on to have severe problems during childhood, including epilepsy, and profound learning and physical disabilities,” continues Professor Greene. “For example, although babies might learn to sit up, most don’t learn to walk or speak more than a few words, and they need help to eat throughout their lives.”
Medicines can help, as can occupational and physical therapies, and support groups can provide families with much-needed information, advice and emotional support, which is particularly important with rare conditions like NKH.
There’s no cure though. While some children have milder forms of NKH that tend to start later, sadly, those with the most severe forms of the condition often die young. Better treatments are needed urgently.
How could this research help?
“We already know what causes NKH,” says Professor Greene. “Children with the condition have abnormalities – or mutations – in genes that code for proteins which act to break down a small molecule called glycine.”
In this project, the team is investigating how these genetic changes lead to symptoms. They aim to learn more about the disease processes that cause seizures and breathing problems by studying changes in brain function. They’re also investigating how well existing treatments work and developing some possible new approaches to treatment.”
“We’re exploring whether an approach called gene therapy is likely to benefit children with NKH,” adds Professor Greene. “Gene therapy would work by putting a normal copy of the gene that is not working into the child’s cells. This would address the genetic changes that are the root cause of all of the symptoms that children experience. At the moment, our work is in the laboratory stages, but we hope it will one day lead to better ways to treat NKH and improve children’s lives.”
1. Orphanet. Glycine encephalopathy. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=407 Website accessed 18 November 2015.
2. Gene Reviews [Internet] Glycine encephalopathy http://www.ncbi.nlm.nih.gov/books/NBK1357/ Website accessed 18 November 2015.
|Project Leader||Professor Nicholas DE Greene MA PhD|
|Project Team||Professor Andrew J Copp DPhil MBBS FRCPathDr Simon N Waddington MSc PhD|
|Project Location||Developmental Biology and Cancer Programme, Institute of Child Health, University College London|
|Project Location Other||Maternal and Fetal Medicine, Institute for Women's Health, University College London|
|Project duration||2 years|
|Date awarded||21 July 2015|
|Project start date||1 January 2016|
|Project end date||30 April 2018|