Organoids for Metabolic Disease Modeling

Inherited metabolic diseases (IMDs) are a diverse group of rare genetic disorders that disrupt metabolic pathways, leading to severe clinical manifestations. Disease models ranging from complex animal models to simple in vitro systems have provided insights into IMDs, but each has limitations. Organoids, three-dimensional in vitro models, bridge this gap by replicating key metabolic functions that are absent in most simple 2D cell models. While organoids do not fully mimic organ complexity, they effectively model disease-specific metabolic defects, as seen in methylmalonic acidemia, Wilson's disease, and cystic fibrosis. Recognizing that function is more critical than organ resemblance, we propose focusing on the specific function of interest rather than selecting a model solely based on its derivation from the most affected organ. Focusing on specific biological processes enables precise, disease-relevant studies that drive novel therapeutic strategies and personalized medicine.