- Since its development five years ago, the research method has identified more than 30 new rare diseases
- The Xenopus diagnostic method can be done in as little as three days as opposed to months
- Latest study discovered a malfunctioning protein called DDX17 causes a rare neurological condition
Scientists have been given a £1.1m grant by the UKRI Medical Research Council (MRC) to continue their life-changing research, after identifying a new disease which causes some children's brains to develop abnormally.
One in 17 people in the UK will suffer from a rare disease at some time in their lives. Most of these rare diseases have a genetic cause and often affect children, but proving which gene change causes a disease is a huge challenge.
To identify the gene, the University of Portsmouth and University of Southampton have been using Xenopus tadpoles as a diagnostic tool since 2020. Since its development, the experimental method has identified more than 30 new rare diseases.
The latest study by the team, published in the journal Brain , discovered that a malfunctioning protein called DDX17 causes the neurological condition. DDX17 is involved in the critical early stage processes that shape neurons in the brain. Up until now, the implication of defects in this protein have been unknown.
Globally, 11 patients were found to have malfunctioning variants of the DDX17 protein. The newly identified condition is characterised by intellectual disability, delays in the development of speech and language, and motor skills.
Now the cause has been identified, it will help clinicians come up with targeted interventions to help patients and their families, also opening the door to screening and prenatal diagnosis.
This discovery was made possible through the use of advanced genomic technologies and extensive global data sharing, with 45 clinicians and scientists from 29 institutes involved worldwide.
This is the latest demonstration of how big data can be combined with lab experiments to make a difference directly to patients. It is a really exciting time to be working in the field of rare diseases. Slowly we are making inroads into the diagnostic odyssey that patients often face.
Professor Matt Guille, Engineering Biology research group at the University of Portsmouth
Study co-author Professor Matt Guille , who leads a laboratory in the Engineering Biology research group at the University of Portsmouth, said: "This is the latest demonstration of how big data can be combined with lab experiments to make a difference directly to patients. It is a really exciting time to be working in the field of rare diseases. Slowly we are making inroads into the diagnostic odyssey that patients often face."
The research team sequenced the DNA of affected patients and their family members, which identified changes to DDX17 as the potential underlying cause of the disease. They discovered that those with the malfunctioning DDX17 protein had the same characteristics as the patients. This showed the link between the protein and disorder very clearly.
Sarah Ennis , Professor of Genomics at the University of Southampton, said: "The Medical Genomics team working on this project are particularly pleased that this finding will enable patients to be given a diagnosis and provide clinical teams with firmer information to guide management."
Studies connecting a gene and a disease are mainly performed in mice, however, experiments in tadpoles have proved just as effective in many cases, and can be done in as little as three days as opposed to months.
Co-author Dr Annie Godwin , from the University of Portsmouth's School of Environment and Life Sciences , said: "The challenge of diagnosis of rare diseases is huge and growing. By using this method to test the link between a genetic change in a patient and the characteristics of their disease we can speed up diagnosis and make it affordable."
Researchers are required by law to replace the use of animals with alternative techniques where possible, to reduce the number of animals used to a minimum, and to refine the way experiments are carried out to make sure animals suffer as little as possible. This is known as the 3Rs.
Professor Guille said: "Whilst everyone strives for a day when this type of experiment can be carried out without using animals at all, it is not yet possible when we need to observe behaviours or assess diseases affecting multiple organs. In these cases we can work to use simpler organisms effectively as we do in this study."
Chris Magee from the not-for-profit organisation Understanding Animal Research added: "This is a great example of how the careful and humane use of animals can have a hugely positive impact on the lives of patients and their carers.
"When people think of research animals, they're probably not thinking about tadpoles, but this work is opening the door to understanding and treating diseases that are extremely difficult to investigate. In vitro methods like cell cultures and organ-on-a-chip are hugely powerful models, but living systems like bodies produce effects from a complex web of interactions that we don't fully understand and struggle to model artificially. It's by using every method available to us, from Big Data, to animals, to all the other tools in the lab, that we're seeing real breakthroughs in diseases once thought to be incurable.
"The scientists involved in this collaboration should be congratulated, not just for their groundbreaking discoveries to date, but for managing to simultaneously drive forward the 3Rs agenda in a way that will enhance animal welfare well into the future."
