Grant: Project Grant

Children with developmental epileptic encephalopathies (DEEs) have frequent seizures and often struggle with learning, attention, and behavior. Many available seizure medicines do not prevent seizures, and even when they do, they can cause side effects like sleepiness, "brain fog," or mood changes, beyond disease-related deficits. We need medicines that both reduce seizures and protect thinking and mood. We developed a new medicine, SN-2000, that targets a brain enzyme called PDE4B. This enzyme turns off a chemical signal (cAMP) that helps brain cells keep their activity stable and supports learning and memory. In mouse models of epilepsy, SN-2000 reduces seizures and improves measures of memory and anxiety. We designed SN-2000 to be selective and allosteric, which means it gently "tunes down" the enzyme rather than shutting it off everywhere, an approach intended to improve tolerability compared with older drugs in the same class. With support from this grant, we will complete early safety tests (called non-GLP toxicology) to find safe dose ranges and check for possible side effects before starting the extensive and costly studies required to test a drug in humans. We will also test whether SN-2000 can help with motivation and memory in mouse models of major depression, a common problem for people living with epilepsy. These studies will tell us whether SN-2000 is ready for the next steps toward clinical trials. If successful, this work will move a new anti-seizure medicine closer to patients and may help children and families by improving daily functioning and quality of life.