Metabolism-based therapies for epilepsy: new directions for future cures

OBJECTIVE: Thousands of years after dietary therapy was proposed to treat seizures, how alterations in metabolism relates to epilepsy remains unclear, and metabolism-based therapies are not always effective.METHODS: We consider the state of the science in metabolism-based therapies for epilepsy across the research lifecycle from basic to translational to clinical studies.RESULTS: This analysis creates a conceptual framework for creative, rigorous, and transparent research to benefit people with epilepsy through the understanding and modification of metabolism.INTERPRETATION: Despite intensive past efforts to evaluate metabolism-based therapies for epilepsy, distinct ways of framing a problem offer the chance to engage different mindsets and new (or newly applied) technologies. A comprehensive, creative, and inclusive problem-directed research agenda is needed, with a renewed and stringent adherence to rigor and transparency across all levels of investigation.