Despite multiple therapeutic strategies, only one gene therapy has successfully reached Phase III clinical trials to date—an AAV2 vector which promotes allotropic ND4 gene expression in patients with Leber’s hereditary optic neuropathy, a primary mitochondrial disease (PMD) associated with point mutations in MT-ND4 [76]. This evidence concerns the gene MT-ND4 and Pelizeaus-Merzbacher spectrum disorder.