Functional Analysis and Rescue of Epilepsy

Why it matters?

Around 1 in 200 children are diagnosed with a genetic epilepsy each year. These children often also have other co-existing conditions such as speech and language problems, migraine and difficulty sustaining attention. In 30% of these children, the current medicines that we have are not effective at stopping their seizures. Many children also suffer some side effects from their epilepsy medicine. In order to understand why medicines don’t work and to develop better ones, we need to understand on a molecular level what is going wrong in the brain to cause epilepsy.

In 2013, our team was part of a European initiative that identified one of the genes that cause many cases of childhood epilepsy associated with speech and language problems. This gene is called GRIN2A and it makes a protein found on the end of nerve cells. We discovered that this gene malfunctions in some cases of Rolandic epilepsy (RE), Landau Kleffner Sydrome (LKS) and Continuous Spikes in Slow-Wave Sleep (CSWSS). In discovering this gene we had started to unlock the puzzle of how epilepsy is caused in certain children.

What we are doing?

In a collaboration with Eli Lilly & Co., Dr Laura Addis is characterising how DNA mutations in the GRIN2A gene from children with epilepsy cause the protein it makes on the end of nerve cells, called an ion channel, to malfunction. Dr Addis will be investigating in cell models what is going wrong by using very powerful microscopes. She will investigate if the ion channels are made from the gene in patients, how they are moved within the cell to its surface when they are mutated, and, if they get to the surface, how they work when they are there when compared to the protein from someone without epilepsy. The second phase of this study is to investigate medicine which can be used to rescue the problems that we are seeing in the mutated ion channels to make them work in a regular way.

Who is conducting the research?

Dr Laura Addis at King’s College London is the principal investigator of this study. Dr Addis is collaborating with scientists at Eli Lilly – Dr Daniel Ursu and Prof. David Collier to carry out this work.

Who can take part?

At this time we are not recruiting individuals for this study as it is primarily based in the laboratory. However, if your child has had genetic testing and is found to have a mutation in the GRIN2A gene then we may contact your family in the future.

Interested?

If you would like to find out more, please contact Dr Addis by email at laura.addis@kcl.ac.uk.

Further Information:

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency – molecular profiling and functional rescue

About our research

We are a research group from King’s College London dedicated to finding the cause of childhood epilepsies. Our research explores the genetics of childhood epilepsy in order to improve the outlook for both diagnosis and treatment.

Publications

Childhoodepilepsy.org has a wide range of research publications, and supporting information documents, for parents of children affected by epilepsy, clinicians and research professionals.

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Neuroimaging and Cognition in Rolandic Epilepsy (CREME)

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Epileptic Encephalopathies Longitudinal Multicentre Omics (DESIRE-ELMO)

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Myoclonic Astatic Epilepsy Study

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Biology of Juvenile Myoclonic Epilepsy (BIOJUME)

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Functional Analysis and Rescue of Epilepsy-Associated GRIN2A Mutations

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Rolandic Epilepsy Genomewide Association International Study (REGAIN)

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Changing Agendas on Sleep, Treatment and Learning in Childhood Epilepsy (CASTLE)

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