Epilepsy: developing a new drug treatment for a rare and debilitating form of the condition

Pyridoxine-dependent epilepsy (PDE) is a rare inherited form of childhood epilepsy that typically appears shortly after birth but can start later in childhood. A child’s seizures are usually controlled with lifelong supplementation with a vitamin called pyridoxine, but many will also have delayed development and learning disabilities. Professor Wyatt Yue is aiming to develop a new drug that can address the root cause of children’s long-term neurological symptoms. He hopes this work will ultimately lead to a new treatment that will greatly improve the lives of children and their families who are affected by this rare and debilitating condition.

This project is jointly funded by Action Medical Research and LifeArc.

How are children’s lives affected now?

Children affected with PDE typically start having seizures soon after birth, which are not controlled with conventional anti-epileptic medications. They may also have other symptoms – such as unusual eye and facial movements – before they develop seizures. Many mothers will remember feeling rhythmic movements in their womb, which are likely to have been the developing baby having seizures.

The ALDH7A1 enzyme, which is faulty in children with PDE, plays a role in breaking down an amino acid called lysine.  This leads to a build-up of toxic chemicals in the child’s body – and the resulting chemical imbalances can lead to seizures, and delayed development and learning disabilities.

“Taking lifelong large daily supplements of pyridoxine can usually control their seizures,” says Professor Yue. “But this doesn’t address the long-term neurological symptoms – and so new treatments are urgently needed to improve the lives of children with PDE and their families.”

How could this research help?

“Our goal is to develop a new drug treatment that can prevent the build-up of the toxic chemical in the body that causes the disease,” says Professor Yue.

The researchers aim to achieve this by lowering the activity of another enzyme, which is responsible for an earlier step in lysine breakdown.  This approach – which is called substrate reduction therapy – has already been successfully applied to other rare diseases.

“We have previously identified several potential drug compounds – and we will now make tiny changes to their chemical structures and evaluate their properties in the laboratory,” says Professor Yue.

The team will then test the effects of the most promising drug candidates in cell studies, selecting the best ones for future development into treatments for patients.

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.