Advances and challenges in modeling Charcot-Marie-Tooth type 2A using iPSC-derived models

Charcot-Marie-Tooth type 2A (CMT2A) is an inherited sensory-motor axonopathy caused by mutations in the Mitofusin2 (MFN2) gene, coding for MFN2 protein. No curative treatment has been developed to date. The advent of induced pluripotent stem cell (iPSC) has provided unprecedented opportunities to understand complex neurological disorders. In CMT2A research, patient-specific iPSCs can be differentiated in motor and sensory neurons, thereby establishing reliable in vitro disease models. Here, we review current available iPSC-based models of CMT2A, focusing on pathogenetic insights derived from these studies and discussing challenges and potential of iPSC-derived models in elucidating disease mechanisms, providing innovative platforms for testing, and developing novel effective therapeutic strategies.