Childhood-onset epilepsy (COE) can be difficult to treat and often comes with cognitive and behavioral challenges. Changes (mutations) in the genes KCNQ2 and KCNQ3, which encode parts of a potassium channel in the brain, are common causes of COE. These mutations can lead to a wide range of epilepsy types—from seizures that resolve on their own in infancy to severe, drug-resistant epilepsy with intellectual disabilities, pointing to a need for treatments beyond just stopping seizures. Also the mutations in these genes vary widely; some reduce channel function (loss of function), others interfere more broadly (dominant negative), while some increase channel activity (gain of function). The type of mutation can influence both the severity of the epilepsy and cognitive development, and the treatment approach.
The BEATKCNQ project is working to improve outcomes for children with these disorders through the facilitation of precision medicine. The project has four key objectives:
- Using advanced computational tools to better predict how each mutation type will affect individual patients, also aiding in clinical trial design.
- Testing existing drugs on lab-grown, patient-specific cell models, using a novel network approach that combines electrical activity measurements and gene expression data to identify potentially effective drugs.
- Finding biomarkers through brainwave (EEG) analysis to predict treatment responses and long-term outcomes.
- Running small, personalized trials to assess if repurposed drugs work in individual cases.
Through these efforts, BEATKCNQ aims to revolutionize care for children with KCNQ2/3-related epilepsy, offering tailored, effective therapies and improving long-term quality of life.