Investigating how calcium channel dysfunction causes epilepsy.
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Dr Marisol Sampedro Castañeda
UCL Queen Square Institute of Neurology
Developmental and epileptic encephalopathies (DEE) are rare but severe childhood epilepsies caused by genetic mutations. Two types – DEE69 and DEE2 – are caused by mutations in different genes, but both appear to disrupt the same protein in the brain called Cav2.3. This protein controls how calcium flows into brain cells, which is essential for regulating brain activity, brain development, and preventing seizures. When Cav2.3 does not properly, it may cause abnormal brain signalling and lead to epilepsy. Despite this, Cav2.3 has not been well studied in epilepsy, and we still do not fully understand how changes in this protein contribute to seizures.
"We know that some gene mutations cause severe epilepsy and neurodevelopmental disorders in children, but our understanding of how symptoms arise is very incomplete. This study will shed light on a specific gene involved in calcium regulation in brain cells, which is affected in at least two forms of genetic epilepsy. Investigating its function, could lead to better management of these conditions and stimulate the development of new drugs aimed at this important target.
This study will explore how Cav2.3 contributes to epilepsy by looking at different mutations. First, the team will test how over 20 mutations in Cav2.3 affect calcium flow and link these changes to symptoms and treatment responses. Next, they will investigate Cav2.3’s role in early brain development, to find out when treatments might be most effective. Finally, they will test if Cav2.3 overactivity causes seizures in DEE2 by using Cav2.3-blocking drugs. These experiments will help to explain how Cav2.3 contributes to epilepsy and whether targeting it could lead to new, more personalised treatments.
This research could explain how changes in Cav2.3 lead to seizures and help identify the best way to treat them. It may lead to more tailored therapies for children with Cav2.3-related epilepsies and reduce the number of medications needed. If successful, this work could quickly guide treatment decisions for affected families and support new uses for existing epilepsy drugs.
