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Mutation-specific therapies aim to correct the underlying mutation through the use of a gene-editing platform or replace the faulty mitochondrial DNA-encoded protein by delivering the wild-type gene using a suitable vector. Recent gene therapy clinical trials assessing the efficacy of allotopically expressed <jats:italic>MT-ND4<\/jats:italic> for the treatment of LHON due to the m.11778G\u2009&gt;\u2009A mutation in <jats:italic>MT-ND4<\/jats:italic> have shown positive results when treated within 12\u00a0months of symptom onset. Mutation-independent therapies can have various downstream targets that aim to improve mitochondrial respiration, reduce mitochondrial stress, inhibit or delay retinal ganglion cell apoptosis, and\/or promote retinal ganglion cell survival. Idebenone, a synthetic hydrosoluble analogue of co-enzyme Q<jats:sub>10<\/jats:sub> (ubiquinone), is the only approved treatment for LHON. Mutation-independent approaches to gene therapy under pre-clinical investigation for other neurodegenerative disorders may have the potential to benefit patients with LHON.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Summary<\/jats:title>\n                <jats:p>Although approved treatments are presently limited, innovations in gene therapy and editing are driving the expansion of the therapeutic delivery pipeline for LHON.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11910-022-01246-y","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T23:04:40Z","timestamp":1669158280000},"page":"881-892","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Developments in the Treatment of Leber Hereditary Optic Neuropathy"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8214-0186","authenticated-orcid":false,"given":"Benson S.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Yu-Wai-Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"1246_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","volume":"30","author":"P Yu-Wai-Man","year":"2011","unstructured":"Yu-Wai-Man P, Griffiths PG, Chinnery PF. 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