Testing A Splice Modulating Oligonucleotide For Treatment Of SCN8A Gain-Of-Function Epilepsies

SCN8A epileptic encephalopathy is a severe, difficult-to-treat pediatric epilepsy caused by mutations in the SCN8A gene that result in the production of an overly active form of the SCN8A protein. Because the SCN8A protein forms a sodium channel important in controlling neuronal excitability, this increase in SCN8A protein activity leads to neuronal hyperexcitability and epilepsy.

To reduce the activity of the SCN8A protein, Dr. Tallent and her team have developed a drug (LSP-SCN8) that directs a process called “alternative splicing” of the SCN8A gene. This process leads to the production of a less functional version of the SCN8A protein, potentially resulting in a decrease in neuronal hyperexcitability. The goal of this project is to test whether this drug can prevent seizures and improve memory, coordination, and survival in a mouse model of SCN8A epileptic encephalopathy