This week’s blog is from Professor Sameer Zuberi, who’s ERUK-funded research investigated new ways to diagnose and treat childhood epilepsies. Prof Zuberi co-chaired last year’s ERUK International Expert Workshop, which explored the links between epilepsy and neurodevelopmental disorders. A year on, Prof Zuberi discusses the impact of the workshop and how far research into this field has come in such a short space of time.
Epilepsy has its highest incidence in early childhood, and around a third of children with epilepsy have seizures that cannot currently be controlled by medication. For many, this can be the beginning of a more complex disorder affecting many aspects of development including learning, speech, language, behaviour and control of movement. Understanding epilepsy and the causes of seizures can provide important insights into all these fundamental aspects of neurodevelopment. Epilepsy management has been focused on controlling seizures, but research is increasingly focused on the causes and mechanisms of the seizures in order to better address problems – such as the learning disability and autism – which share those same causes.
Alongside Professor Stuart Cobb (University of Edinburgh) and Professor Oscar Marin (Kings College, University of London), it was a pleasure to curate ERUK’s 2019 International Expert Workshop. The event was held in St Anne’s College Oxford and brought together researchers from all over the world to discuss the links between epilepsy and neurodevelopment. Following on from the workshop, the ‘Special Issue’ of the European Journal of Paediatric Neurology was published in January 2020 to ensure the learnings from the workshop were shared widely.
Held exactly a year before the UK went into lockdown, the workshop now seems from a different age, with researchers having not met in person for the last six months. It might appear that most clinical and research activities not related to tackling the Covid-19 pandemic have been put on hold. I certainly know of colleagues working in laboratories whose experiments, some in genesis for months, had to be abandoned. In preparing for this blog, I looked back at the ‘Special Issue’ from January 2020 in which papers based on the presentations at Oxford were published. From recent developments, it is clear that not all research has been put on hold and that despite the challenges of the pandemic, researchers have not stopped pushing the boundaries of knowledge.
At the workshop, Professor Scott Baraban, from the University of California, explained how his team had developed models for genetic childhood epilepsies in zebrafish and were able to rapidly test potential anti-seizure medications by putting them in the water in which the fish swam. Testing in the Baraban lab has led to a human trial of a promising anti-seizure treatment called clemizole hydrochloride, which began in July this year and aims to treat severe childhood epilepsy.
Several presentations at the ERUK International Expert Workshop focused on the prospects of genetic-based therapies in epilepsy. If you had asked me 5 or 10 years ago whether this would become a reality in the following decade, I could not have seen a clear path to success – luckily, there are many neuroscientists with better vision than me. There are a group of epilepsies called the developmental and epileptic encephalopathies (DEEs) which begin in early infancy and in which at least half a genetic cause can now be tested for and diagnosed. These are conditions in which epilepsy and the underlying cause both contribute to a learning disability. If the genetic defect can be treated there is the prospect of not only stopping the seizures but also preventing the learning disability. The most common severe genetic epilepsy is Dravet syndrome, which is due to genetic changes preventing enough of a protein called SCN1A being made. This protein helps control electrical signalling in the brain. In August 2020, the first child was treated with a compound called STK-001 which acts to increase the amount of SCN1A protein made in brain cells. This could be a landmark moment in the treatment of genetic epilepsies.
As a paediatric neurologist, I see many children with genetic epilepsies. Our ERUK-funded work in Scotland has shown that these epilepsies are not very rare; they affect about 1 in 2,000 children. When we inform families of the diagnosis, we have to be honest about what we think the future will hold in terms of a child’s neurodevelopment, but it is also important to give families hope for the future. Research into epilepsy is proving the best way to make that hope a reality.
-Professor Sameer Zuberi
Read more about the ERUK International Expert Workshop on Epilepsy and Neurodevelopmental Disorders here.
Find more on the publication of Special Issue of the European Journal of Paediatric Neurology here.
Read more about Professor Sameer Zuberi’s ERUK-funded research investigating new ways to diagnose and treat childhood epilepsies here.