ubiquinone and Blindness

Topics: Blindness; Humans; Mitochondria; Optic Atrophy, Hereditary, Leber; Ubiquinone

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance.. We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.. The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.. The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON.

Topics: Antioxidants; Blindness; DNA Copy Number Variations; DNA, Mitochondrial; Female; Genes, Mitochondrial; Humans; Male; Mitochondria; Mitochondrial Diseases; Mutation; Optic Atrophy, Hereditary, Leber; Pedigree; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Ubiquinone; Visual Acuity

To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures.. Open-label clinical trial.. University medical center. Patients  Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention  During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose).. Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls.. Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded.. In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.

Topics: Adolescent; Blindness; Child; Chromatography, High Pressure Liquid; Color Vision; Drug Approval; Emergency Medical Services; Eye; Female; Humans; Longitudinal Studies; Male; Middle Aged; Mitochondrial Diseases; Optic Atrophy, Hereditary, Leber; Retina; Tandem Mass Spectrometry; Tomography, Optical Coherence; Ubiquinone; United States; United States Food and Drug Administration; Visual Acuity; Visual Field Tests; Young Adult