CLDF announces three research grants and invites new applications
Children’s Liver Disease Foundation (CLDF) has awarded grants to three new research projects.
Genome editing liver organoids for treatment of liver disease – University of Oxford, Dr Deborah Gill
This study, led by Dr Deborah Gill, is looking at paediatric liver diseases caused by genetic mutations (such as alpha-1 antitrypsin deficiency or Wilson’s disease). One approach to tackling such conditions is to deliver a working copy of the gene to cells in the liver. This approach, sometimes called ‘gene addition’, works only temporarily, because as the liver grows and the treated liver cells divide the new gene is eventually lost. In this study, the researchers propose a strategy whereby the working copy of the gene is inserted into the DNA of the cells in the liver using a form of genome editing. This means that the benefits of the working copy of the gene can be realised over a much longer period of time.
This research is valuable as it has the potential to address the genetic cause of some liver diseases. The team has already demonstrated that this genome editing approach can work in human liver cell lines, but will now have the opportunity to perform these studies in small artificial livers (known as liver organoids) in order to develop the approach.
Identification of biomarkers in paediatric fatty liver disease – Addenbrooke’s Hospital
The research team, led by Dr Jake Mann, will use blood samples from children who had had liver biopsies for fatty liver disease and run two tests on them: ELF (enhanced liver fibrosis score) and lipidomics (looking in detail at all the fats in blood). The results of the blood tests will be compared to the liver biopsy results to see whether the ELF and lipidomics test could be used instead of the biopsy.
The research is valuable because fatty liver disease is the most common liver condition affecting children. At the moment, it is impossible to tell how severe the liver damage is without doing a liver biopsy, which can have risks, be expensive and requires a general anaesthetic. Some guidelines from the UK have suggested using a blood test (‘ELF’) to predict how severe fatty liver disease is, with the aim of avoiding a biopsy.
However, while the ELF and lipidomics have proved useful in testing adults with fatty liver disease, neither has been used to any great degree with children so it is hard to know how effective the tests are. The aim of the project is to see whether blood tests could replace liver biopsies when finding out whether liver damage has been caused by fatty liver disease and if so, how damaged the liver is.
The results could lead to fewer paediatric patients requiring a liver biopsy.
Diagnosis of covert hepatic encephalopathy in young people with biliary atresia: a feasibility study – King’s College Hospital
This project, led by Dr Marianne Samyn, is looking at hepatic encephalopathy, a complication of liver disease. When the liver is damaged and unable to remove harmful toxins from the blood, such substances build up in the blood stream and can cause changes in the brain. This can result in both physical and mental symptoms such as confusion, forgetfulness, sleepiness and personality changes.
A milder version called covert hepatic encephalopathy exists. However, it is more difficult to identify as it is characterised by more subtle changes. In adults, a variety of neuro-psychological and neuro-physiological tests are used to diagnose covert hepatic encephalopathy. The aim of this study is to determine whether the tests used in adults can be adapted for use in children and young people.
Due to the lack of research into covert hepatic encephalopathy in children and young people, it isn’t known how prevalent it is or how it affects children and young people with chronic liver disease in their daily activities, including education and employment.
If adult tests can be used for children and young people, it will make the condition easier to diagnose and could affect the treatments offered to those who are experiencing it.
2018 grant round
CLDF is now inviting applications for its 2018 grant round. The charity supports UK based preliminary research (up to £10,000 per award) that will contribute significantly to a subsequent larger research grant proposal. Aside from the need to address liver disease in children, there are no restrictions on the scope of projects, which may focus on gaining insights into the causes of liver disease or improving diagnosis, management and longer-term outcomes. Awards can include basic, translational, laboratory, clinical or a social science focus.
Applications must be received by June 25th 2018. Click here for further information.