MT-ND4 and Leber hereditary optic neuropathy: Preclinical studies have demonstrated that recombinant AAV2 with wild type ND4 can rescue ATP production in cultured fibroblasts isolated from ND4-LHON patients, and that the therapeutic ND4 protein could successfully integrate into complex I in induced LHON models, preventing RGC apoptosis and optic nerve atrophy [68].