COMPREHENSIVE TREATMENT PLATFORM FOR CHILDREN WITH DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES (TREAT|DEE)

Epilepsy affects approximately 50 million people worldwide and is one of the most common neurological disorders. The term “epilepsy” encompasses a diverse group of rare diseases, many with genetic and/or structural causes. Incidence is particularly high in early childhood, where seizures can severely disrupt neurodevelopment or lead to premature death.
Developmental and epileptic encephalopathies (DEEs) are among the most severe pediatric epilepsies, characterized by early-onset seizures and profound developmental impairment. DEEs are clinically and genetically heterogeneous, and conventional anti-seizure medications frequently fail to achieve seizure control or improve long-term outcomes, highlighting an urgent need for precision therapies. Although advances in genomic technologies have accelerated the discovery of epilepsy-associated genes, many children with DEEs remain without a genetic diagnosis, and the phenotypic spectrum of many known disease-causing variants remains incompletely defined.
Defining DEE phenotypes has been central to our previous work.By analyzing germline and somatic variants, we have identified genetic epilepsy causes and characterized their phenotype spectrum, particularly for variants in the genes TRPM3, WWOX, and TULP4, characterized disease mechanisms, and identified novel DEE-targeted medications such as primidone for TRPM3-DEE.
In TREAT|DEE, we aim to develop an integrated gene- and mechanism-targeted precision medicine platform for children with rare, drug-resistant epilepsies such as DEEs. By combining comprehensive genomic analysis with high-throughput drug screening, we seek to identify and prioritize targeted therapies for preclinical and clinical evaluation, including N-of-1 trials. This patient-centered approach aims to improve seizure control, neurodevelopmental outcomes, and quality of life in this vulnerable population.