Developing a cutting-edge treatment for a severe form of epilepsy that affects children

Many early-onset epilepsies are caused by changes in genes that arise for the first time in an affected individual, including in a gene called EEF1A2. Most children affected with EEF1A2-related neurodevelopmental disorder will develop severe epilepsy within their first year – and many will also have delayed development, learning difficulties, behavioural or movement problems. Professor Cathy Abbott of the University of Edinburgh is investigating an innovative approach called antisense oligonucleotide therapy (ASO therapy) that can precisely target the underlying cause of the disease. She hopes her laboratory work could ultimately lead to an effective new treatment that can help control seizures and prevent disability – improving the quality of life for children and their families affected by this devastating condition.

How are children’s lives affected now?

EEF1A2-related neurodevelopmental disorder is a rare condition caused by faults that arise in the EEF1A2 gene, which contains the instructions to make a protein. These faults lead to harmful changes to the EEF1A2 protein that affect how it works in nerve and muscle cells.

“Although the symptoms can vary between affected children, many will experience repeated seizures every day that start within the first four months of life,” says Professor Abbott. “They will also usually start missing their developmental milestones – and most will never learn to talk, have movement difficulties and sleep badly.”

Although most individuals known to have faults in the EEF1A2 gene are children, young adults with changes in this gene can also develop movement disorders and might even lose any ability to walk that they had.

“Sadly, current medications are often ineffective at controlling seizures – and they do not address the root causes of the condition,” says Professor Abbott. “Effective new treatments are badly needed that can help improve the lives of children with EEF1A2-related neurodevelopmental disorder.”

How could this research help?

“Our long-term goal is to develop a new type of treatment that can help to alleviate seizures and disability in children with this severe epilepsy disorder,” says Professor Abbott.

ASO therapy is a cutting-edge approach that uses small molecules to precisely switch off the activity of a faulty gene in affected cells.  It is showing promise for treating other neurological disorders – including another severe type of epilepsy affecting children.

“Using ASO therapy to switch off the faulty EEF1A2 gene in nerve and muscle cells could be an effective way to block the production of the damaging EEF1A2 protein,” says Professor Abbott.

The researchers will design, make and test a series of different ASO therapies targeting a specific fault in the EEF1A2 gene to discover if any can successfully reduce the levels of the faulty EEF1A2 protein in laboratory models.

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