Methods for Elucidating Disease Mechanisms in Neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) affect 317 million children and young people globally. While NDDs are a diverse group of disorders that impact multiple organ systems, epilepsy, autism spectrum disorder (ASD), and/or intellectual disability (ID) are common outcomes. Unfortunately, there are few disease-modifying therapies and no cures for NDDs. Recently, however, gene editing, cellular/molecular assays, and stem cell models have emerged as promising techniques to deeply understand the root causes of NDD, categorize genetic variants, and more precisely model human disease processes. Additionally, several techniques, particularly gene editing, have already had clinical success. In this review, we detail several novel methods for functionally validating genetic variants, stem cell models of NDDs, and novel gene editing approaches. Understanding and applying these methods is crucial for uncovering novel disease mechanisms and therapeutic targets for NDDs, as well as for advancing technical approaches from the bench to the clinic.