Charcot Marie Tooth (CMT) disease is a rare and incurable genetic disease of the Peripheral Nervous System resulting from defects in Schwann cells (demyelinating CMT) or in motor/sensory neurons (axonal CMT). More than 120 causative CMT-related genes have been identified so far. Among them, CMT type 2A is the most common axonal form and is linked to mutations in the MFN2 gene encoding Mitofusin-2 (MFN2). MFN2 is an important regulator of mitochondrial fusion. Around a hundred mutations have been described and are distributed throughout all the protein's domains. Consequently, gene therapy strategies targeting of a given mutated allele cannot offer large-scale therapeutic prospects. The majority of histopathological defects linked to mutated MFN2 are reproduced by the loss of MFN2 in affected neurons. Based on this, an overexpression of wild-type MFN2 in affected neurons could attenuate CMT2A pathology. This could be achieved using the adequate combination of AAV vectors and neuronal promoters. We intend to test a strategy for increasing MFN2 levels, using in vitro (IPS-derived motor neurons from CMT2A patients) and in vivo (MFN2R94Q mice) preclinical models. In vitro, we showed that AAV6-hSyn-MFN2WT restores proper mitochondrial shape, neuronal activity as well as neurite length, originally modified in CMT2A IPSC-derived MNs. In vivo, intrathecal injection of AAV9-hSyn-MFN2WT improved locomotion (rotarod), as well as axonal pathology (Stathmin2 expression, a mediator of axonal repair) in the tibial nerve of CMT2A mice. We showed that the MFN2WT overexpression in neurons improved CMT2A pathology and could be a promising therapeutic approach for CMT2A.