Updated on
What did the project achieve?
Vici syndrome is a very rare and severe genetic condition that affects many different parts of the body – often causing heart problems, delayed development, neurodegeneration and seizures, and repeated infections. Sadly, there are currently no effective treatments for children with this debilitating condition – and it will severely shorten their lives.
“Our laboratory research has improved understanding of the underlying biological processes behind this condition,” says Professor Michael Duchen of University College London. “This work could ultimately lead to new treatments to help reduce the impact of Vici syndrome, and other related devastating diseases, on children and their families.”
Vici syndrome is caused by faults in the EPG5 gene, which provides instructions for making a protein that plays a key role in a process called autophagy – a system which cells use to clear away old or damaged material. The team previously discovered that patient skin cells have problems with their mitochondria – the tiny structures that generate energy within cells. They also found that these faulty mitochondria are especially vulnerable to damage triggered by normal cell activity, causing them to release molecules that can ultimately lead to cell death.
To explore this further, the team carried out experiments on nerve cells generated from stem cells that had been reprogrammed from patient skin cells.
“We found that the same problems we saw in patient skin cells also occur in nerve cells,” says Professor Duchen. “A similar chain of events leads to nerve cell damage and death, helping to explain the neurodegeneration and seizures experienced by children with Vici syndrome.”
Importantly, the researchers identified several biological pathways that could potentially be targeted with drugs.
“Our early laboratory studies have shown that drugs aimed at these pathways could restore cell function in these cell models,” says Professor Duchen. “This opens exciting new possibilities for developing treatments for children with Vici syndrome – and potentially for other diseases involving disrupted autophagy – in the future,” says Professor Duchen.
This research was completed on
How are children’s lives affected now?
Children with Vici syndrome experience a wide variety of symptoms affecting almost any part of the body. They will often have heart problems, delayed development, progressive deterioration of the nervous system and seizures and repeated infections due to problems with their immune system.
“Vici syndrome will profoundly affect a child’s quality of life,” says Professor Duchen. “Sadly, there are currently no effective treatments for children with this extremely debilitating condition and it will severely shorten their lives.”
Vici syndrome is caused by faults in the EPG5 gene, which carries the instructions to make a protein that plays a key role in a process that enables cells to dispose of aging or damaged materials. The team has recently discovered that the mitochondria in patient skin cells do not function properly, revealing potential new strategies for treating the disease.
This knowledge could help identify effective new treatments that could transform the lives of children with Vici syndrome and their families
How could this research help?
“Our ultimate aim is to identify medicines that are already used to treat other diseases that could be repurposed for patients with Vici syndrome,” says Professor Duchen.
The researchers will now investigate whether poorly functioning mitochondria also contribute to the deterioration of the nervous system and seizures that affect children with Vici syndrome.
“We will carry out a series of laboratory experiments to study the effects of the faulty EPG5 gene on patient-derived nerve cells, with a focus on mitochondrial function,” says Professor Duchen.
The team will test several existing drugs to find out whether they can help to restore mitochondrial function in patient-derived nerve cells in the laboratory.
“We hope this will one day lead to treatments that might benefit not only children with Vici syndrome but that might also benefit people with several other conditions in which similar processes are involved and for which no effective treatments are yet available,” says Professor Duchen.
Research table
Project details
| Project Leader | Professor Michael R Duchen BA PhD FRCP MAE |
| Location | Department of Cell and Developmental Biology, University College London |
| Project Team | Dr Kritarth Singh, BSc MSc PhD |
| Grant Awarded | |
| Grant Amount | £199,171 |
| Start Date | |
| End Date | |
| Duration | 30 months |
| Grant Code (GN number) | GN2959 |
We do not provide medical advice. If you would like more information about a condition or would like to talk to someone about your health, contact NHS Choices or speak to your GP.