TreatKCNQ - Gezielte Behandlung von KCNQ-Enzephalopathien: Retigabin-Analoga, Wirkstoffrepurposing und allelspezifischer Knockdown. Teilvorhaben: Validierung von Retigabin- Analoga und Repurposed Compounds in primären Mausneuron- und humanen Hirnschnitt Kulturen

01.06.2021 bis 31.05.2024

KCNQ-associated encephalopathies (KCNQ-E) are a group of severe epilepsies with onset in the first months of life, characterized by treatment resistant seizures and developmental delay. They are caused by mutations in genes encoding voltage-gated potassium channels that are responsible for the M-current, which plays a critical role in the regulation of neuronal excitability. Both a severe lack and excess of channel function can result in the development of KCNQ-E. Seizures in children with KCNQ-E often respond poorly to anti-epileptic drugs, and more importantly, therapies for the developmental problems are currently unavailable. With the aim to develop improved therapies for KCNQ-E, we will establish a consortium of researchers with expertise in KCNQ-related pathology and drug development, and access to a set of disease-relevant assays and models. We expect to provide pre-clinical evidence for different types of targeted treatments that have the potential to improve the developmental outcome of KCNQ-E.