In vitro proof of concept study for RNA interference as a treatment for KCNQ2 encephalopathy.

Epilepsy is the forth most common neurological disorder, affecting around 50 million of people worldwide. The epileptic encephalopathies (EEs) are a heterogeneous subgroup of severe epilepsies with onset in the first years of life, which are characterized by treatment resistant seizures and developmental slowing or regression. The majority of EEs have a monogenic basis, and recent advances in gene discovery have greatly increased our neurobiological insights in these disorders. KCNQ2 encephalopathy, caused by mutations in the gene KCNQ2 as described in our research group, is the prototype and most frequent form of EE with neonatal onset. Seizures in these patients often respond poorly to the available anti-epileptic drugs, and more importantly, therapies targeting the neurodevelopmental problems are currently unavailable. In this project we aim to provide evidence for a targeted treatment strategy that has the potential to improve the developmental outcome of these patients. Using neuronal cultures derived of blood cells from patients with KCNQ2 encephalopathy as a disease model, we will study the treatment potential of RNA interference, a biological process that can be exploited to reduce the expression of a disease causing allele. Doing so, we aim to reverse both the epileptic and neurodevelopmental features of EEs. If successful, such an approach can be extended to many more EEs with similar characteristics.

Keywords:MODEL SYSTEMS

Disciplines:Genetics, Systems biology, Molecular and cell biology