Treatment of Leber Hereditary Optic Neuropathy
Leber hereditary optic neuropathy (LHON) is a primary mitochondrial DNA (mtDNA) disorder characterised by bilateral, painless, subacute, central visual loss. The majority of patients harbour one of three mtDNA point mutations (m.3460G>A, m.11778G>A and m.14484T>C) with the m.11778G>A mutation being the most common cause of LHON worldwide. This mitochondrial optic neuropathy is characterised by the preferential early loss of retinal ganglion cells (RGCs) within the papillomacular bundle, which accounts for the dense central or caecocentral scotoma observed in this disorder. The management of LHON remains largely supportive, but rapid advances in drug discovery and genetic engineering are paving the way for more targeted strategies aimed at rescuing RGCs and improving the visual prognosis. Although a number of ethical and scientific concerns have been raised that need to be addressed further, mitochondrial replacement therapy offers the hope of preventing the maternal transmission of mtDNA LHON mutations for female carriers of childbearing age who wish to have their own biological children.
KeywordsGene therapy Idebenone Leber hereditary optic neuropathy Mitochondrial donation Neuroprotection Retinal ganglion cell
PYWM is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK), and also receives funding from Fight for Sight (UK), the Isaac Newton Trust (UK), the UK National Institute of Health Research (NIHR) as part of the Rare Diseases Translational Research Collaboration, and the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. BLL is supported in part by a National Eye Institute grant (U10 EY023558-01A1) and by the Robert Z. and Nancy J. Greene Chair in Ophthalmology, Bascom Palmer Eye Institute, University of Miami. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Conflicts of Interest
PYWM holds a consultancy agreement with GenSight Biologics (Paris, France).
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