Leber hereditary optic neuropathy is a mitochondrial disease mainly due to pathologic mutations in mitochondrial genes related to the respiratory complex I of the oxidative phosphorylation system. Genetic, physiological, and environmental factors modulate the penetrance of these mutations. We report two patients suffering from this disease and harboring a m.15950G > A mutation in the mitochondrial DNA-encoded gene for the threonine transfer RNA. We also provide evidences supporting the pathogenicity of this mutation.
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| http://dx.doi.org/10.1111/cge.14189 | DOI Listing |
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Nanomedicine (Lond)
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Department of Bioengineering, King Fahd University of Petroleum and Minerals (KFUPM), Dhahran, Saudi Arabia.
Leber's congenital amaurosis (LCA) represents a set of rare and pervasive hereditary conditions of the retina that cause severe vision loss starting in early childhood. Targeted treatment intervention has become possible thanks to recent advances in understanding LCA genetic basis. While viral vectors have shown efficacy in gene delivery, they present challenges related to safety, low cargo capacity, and the potential for random genomic integration.
View Article and Find Full Text PDFClinical trials in Leber hereditary optic neuropathy: outcomes and opportunities.
Curr Opin Neurol
December 2024
Department of Ophthalmology, Emory University School of Medicine.
Purpose Of Review: Leber hereditary optic neuropathy (LHON) is a mitochondrial DNA disease characterised by sequential bilateral vision loss due to loss of retinal ganglion cells. The purpose of this review is to provide an update on the results of recent clinical trials for LHON, focusing on studies of idebenone and lenadogene nolparvovec gene therapy.
Recent Findings: Evidence from three clinical studies (RHODOS, RHODOS-OFU, and LEROS) suggest that idebenone should be started early and continued for at least 24 months.
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Hereditary optic neuropathies, including dominant optic atrophy and Leber's hereditary optic neuropathy, are genetic disorders characterized by retinal ganglion cell degeneration leading to vision loss, mainly associated with mitochondrial dysfunction. In this study, we analysed mitochondrial distribution and ultrastructure in the retina and longitudinal optic nerve sections of pre-symptomatic hereditary optic neuropathies mouse models with Opa1 and Nd6 deficiency to identify early mitochondrial changes. Our results show significant mitochondrial fragmentation and increased mitophagy in mice, indicating early mitochondrial changes prior to neuronal loss.
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