Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials

Amyotrophic lateral sclerosis (ALS) is a terminal complex neurodegenerative disease, with 10%-15% of cases being familial and the majority being sporadic with no known cause. We lack models for the 85-90% sporadic ALS cases. More creative, sophisticated models of ALS disease are required to unravel the mysteries of this complicated disease. While ALS patients require new medications and treatments urgently, suitable pre-clinical in vitro models for drug screening are lacking. Therefore, human-derived induced pluripotent stem cell (hiPSC) technology offers the opportunity to model diverse and unreachable cell types in a culture dish. In this review, we focus on recent hiPSC-derived ALS neuronal and non-neuronal models to examine the research progress of current ALS 2D monocultures, cocultures, and more complex 3D-model organoids. Despite the challenges inherent to hiPSC-based models, their application to preclinical drug studies is enormous.