Reversibility and therapeutic development for neurodevelopmental disorders, insights from genetic animal models

Abstract

Neurodevelopmental Disorders (NDDs) encompass a broad spectrum of conditions resulting from atypical brain development. Over the past decades, we have had the fortune to witness enormous progress in diagnosis, etiology discovery, modeling, and mechanistic understanding of NDDs from both fundamental and clinical research. Here, we review recent neurobiological advances from experimental models of NDDs. We introduce several examples and highlight breakthroughs in reversal studies of phenotypes using genetically engineered models of NDDs. The in-depth understanding of brain pathophysiology underlying NDDs and evaluations of reversibility in animal models paves the foundation for discovering novel treatment options. We discuss how the expanding property of cutting-edge technologies, such as gene editing and AAV-mediated gene delivery, are leveraged in animal models for the therapeutic development of NDDs. We envision opportunities and challenges toward faithful modeling and fruitful clinical translation.