Novel advanced patient-derived in vitro models of pediatric movement disorders to develop personalized therapeutic
Scarlett Yeadon1, Ainara Salazar-Villacorta1,2,3, Manju A Kurian1,3
1Department of Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, GOS-Institute of Child Health, University College London, London, United Kingdom.
Abstract:
Pediatric movement disorders (PMDs) are genetically and phenotypically heterogeneous neurodevelopmental and neurodegenerative conditions for which disease-modifying therapies remain limited, in part due to the poor translational relevance of traditional animal and cellular models. Recent advances in complex patient-derived in vitro systems, including regionally patterned neuronal cultures, organoids, assembloids, and microfluidic platforms, enable the study of human disease while preserving the patient's inherent genetic background. These models facilitate direct examination of pathogenic mechanisms, circuit-level dysfunction and therapeutic strategies, thereby offering new opportunities to advance precision medicine. This review synthesizes recent progress in patient-derived neural models relevant to PMDs, highlighting emerging technologies that increase biological and physiological complexity, and discusses key technical and translational challenges.
