ubiquinone and Optic-Atrophy--Hereditary--Leber

To review recent therapeutic advances in Leber hereditary optic neuropathy (LHON).. Idebenone, a synthetic analog of ubiquinone (Coenzyme Q10) is an antioxidant and component of the mitochondrial electron transport chain. Since the initial approval of the drug in 2015 in Europe, recent trials have evaluated its role as prolonged treatment in LHON. Gene therapy has recently emerged as a promising alternative for the treatment of LHON. Among several investigations, RESCUE and REVERSE are two phase 3 clinical trials of gene therapy in patients with LHON in early stages. Results in these trials have shown a bilateral visual acuity improvement with unilateral intravitreal injections at 96 weeks and sustained visual improvement after 3 years of treatment. The most recent REFLECT phase 3 clinical trial in LHON has shown significant improvement of vision after bilateral intravitreal injections compared with the group that received unilateral injections.. Historically, LHON has been considered an untreatable disease, but recent developments show that new pharmacological and gene therapy approaches may lead to visual recovery. Further studies are needed to support these data.

Topics: Antioxidants; Clinical Trials, Phase III as Topic; DNA, Mitochondrial; Genetic Therapy; Humans; Optic Atrophy, Hereditary, Leber; Ubiquinone; Visual Acuity

The purpose of this review is to present the current and emerging treatment alternatives for Leber's hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.. A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.. Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.. The treatment of LHON remains challenging, given the nature of the disease and its prognosis.

Topics: Antioxidants; Genetic Therapy; Humans; Optic Atrophy, Hereditary, Leber; Stem Cell Transplantation; Treatment Outcome; Ubiquinone

Topics: Antioxidants; Clinical Trials as Topic; Friedreich Ataxia; Humans; Optic Atrophy, Hereditary, Leber; Ubiquinone

Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients. Idebenone (Raxone®) is approved by the European Medicines Agency for the treatment of LHON and has been available on the European market since 2015. Due to its molecular mode of action of bypassing the defective mitochondrial complex I, idebenone leads to improved energy supply and a functional recovery of retinal ganglion cells during the acute stage of the disease, thereby preventing further vision loss and promoting recovery of vision. Thus, commencing treatment shortly after the onset of symptoms is likely to have the best therapeutic effect, a hypothesis that is supported by the available clinical data.

Topics: Antioxidants; Humans; Optic Atrophy, Hereditary, Leber; Ubiquinone

To discuss recent advances in potential treatments for Leber hereditary optic neuropathy (LHON), a typically visually devastating hereditary optic neuropathy caused by mutations in the mitochondrial genome.. Idebenone has been proposed as a means of bypassing defective complex I activity and a free radical scavenger to prevent oxidative damage. EPI-743 may have more potency than idebenone, but no clinical trials have been performed. Gene therapy techniques have advanced significantly, including allotopic expression and nuclear transfer. Successful rescue of animal models of LHON with both of these therapies has been demonstrated. Introduction of exogenous DNA into the mitochondrial genome with mitochondrial targeting of viral vectors is another promising technique.. There are currently no proven treatments for LHON. However, there are many promising novel treatment modalities that are currently being evaluated, with several clinical trials underway or in the planning stages. Supportive measures and genetic counseling remain of great importance for these patients.

Topics: Animals; Genetic Counseling; Genetic Therapy; Humans; Mitochondria; Optic Atrophy, Hereditary, Leber; Ubiquinone

Leber's hereditary optic neuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried.

Topics: Antioxidants; DNA, Mitochondrial; Genetic Predisposition to Disease; Humans; Molecular Diagnostic Techniques; Mutation; Optic Atrophy, Hereditary, Leber; Ubiquinone

Many human childhood mitochondrial disorders result from abnormal mitochondrial DNA (mtDNA) and altered bioenergetics. These abnormalities span most of the mtDNA, demonstrating that there are no "unique" positions on the mitochondrial genome that when deleted or mutated produce a disease phenotype. This diversity implies that the relationship between mitochondrial genotype and clinical phenotype is very complex. The origins of clinical phenotypes are thus unclear, fundamentally difficult-to-treat, and are usually clinically devastating. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and mortality. Vitamin supplements and pharmacological agents have been used in isolated cases and clinical trials, but the efficacy of these interventions is unclear. In spite of recent advances in the understanding of the pathogenesis of mitochondrial diseases, a cure remains elusive. An optimal cure would be gene therapy, which involves introducing the missing gene(s) into the mitochondria to complement the defect. Our recent research results indicate the feasibility of an innovative protein-transduction ("protofection") technology, consisting of a recombinant mitochondrial transcription factor A (TFAM) that avidly binds mtDNA and permits efficient targeting into mitochondria in situ and in vivo. Thus, the development of gene therapy for treating mitochondrial disease offers promise, because it may circumvent the clinical abnormalities and the current inability to treat individual disorders in affected individuals. This review aims to focus on current treatment options and future therapeutics in mitochondrial disease treatment with a special emphasis on Leber's hereditary optic neuropathy.

Topics: Animals; Antioxidants; Dietary Supplements; Disease Models, Animal; DNA-Binding Proteins; DNA, Mitochondrial; Female; Genetic Therapy; Humans; Male; Mitochondria; Mitochondrial Proteins; Mutation; Optic Atrophy, Hereditary, Leber; Oxidative Stress; Phenotype; Recombinant Proteins; Transcription Factors; Ubiquinone

A 31-year-old woman developed subacute bilateral visual loss over a 2-week period. Two months later, the diagnosis of Leber hereditary optic neuropathy (LHON) 11778/ND4 was established and the patient was treated with 900 mg of idebenone daily. Over the ensuing 9 months, visual acuity improved from 20/200 to 20/25 in each eye with near-total resolution in visual field abnormalities. Our case report is in agreement with 2 large published series of patients with LHON treated with idebenone, raising hope for treatment of this visually devastating mitochondrial disorder.

Topics: Adult; Antioxidants; Clinical Trials as Topic; Female; Humans; Optic Atrophy, Hereditary, Leber; Prospective Studies; Recovery of Function; Retrospective Studies; Treatment Outcome; Ubiquinone

The purpose of the study was to present results from a national Dutch cohort of patients with Leber's Hereditary Optic Neuropathy (LHON) treated with idebenone.. The multicentre, open-label, retrospective evaluation of the long-term outcome of idebenone treatment of Dutch LHON patients on visual function and on thickness of the retinal ganglion cell layer. Patients included in the analysis had a confirmed mutation in their mitochondrial DNA encoding either of the seven subunits of complex I, had a reported loss of vision in at least one eye and had a follow-up of more than 6 months after their treatment was started. Control visits involved routine clinical examinations of visual function and retinal structure at (1) the start of treatment, (2) nadir (time of lowest visual acuity), (3) the time of recovery (if any), (4) the time of termination of treatment and (5) more than 6 months after termination of the treatment.. Data from 72 patients were analysed. Treatment duration was 23.8 ± 14.4 (mean ± SD) months. A positive response, that is either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS), occurred in 53% and 11% of the patients, respectively. The magnitude of CRR was 0.41 ± 1.54 logMAR. CRR of visual acuity is associated with recovery of colour discrimination. The thickness of both the ganglion cell complex (GCC) and the retinal nerve fibre layer (RNFL) is irreversibly reduced.. Our results confirm that idebenone may help to restore or maintain visual function. Whether this effect will persist is still unknown. Thinning of retinal neural tissue appears to be permanent.

Topics: Antioxidants; Cohort Studies; Humans; Netherlands; Optic Atrophy, Hereditary, Leber; Retrospective Studies; Treatment Outcome; Ubiquinone

Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse.. Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed.. At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor.. These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

Topics: Adolescent; Adult; Aged; Antioxidants; Child; Female; Follow-Up Studies; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Retrospective Studies; Time Factors; Treatment Outcome; Ubiquinone; Visual Acuity; Young Adult

The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON.. Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months.. Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain.. This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss.

Topics: Adolescent; Adult; Antioxidants; Color Perception; Double-Blind Method; Female; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Pigmentation Disorders; Skin Diseases, Genetic; Treatment Outcome; Ubiquinone

Topics: Adolescent; Adult; Aged; Cohort Studies; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Time Factors; Treatment Outcome; Ubiquinone; Visual Acuity; Young Adult

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

Topics: Adolescent; Adult; Aged; Antioxidants; Contrast Sensitivity; DNA, Mitochondrial; Double-Blind Method; Female; Humans; Male; Middle Aged; Mutation; Optic Atrophy, Hereditary, Leber; Placebos; Prospective Studies; Retina; Ubiquinone; Visual Acuity; Young Adult

To investigate the effect of Wuzi Yanzong Decoction (WYD) in treating Leber hereditary optic neuropathy (LHON).. Thirty patients of LHON up to the requirement were assigned to two groups, the treated group administered with WYD plus coenzyme Q10, and the control group with coenzyme Q10 alone, all for 3 months. Patients' visual acuity, visual field, vision evoked potential (VEP) and their Chinese medicine syndrome were observed before and after treatment.. After treatment, all the above-mentioned indexes were improved to some extents in the treated group, but showed no evident change in the control group excepting visual acuity, comparison between groups showed the differences were significant in all items.. WYD shows certain clinical therapeutic effect for treatment of LHON.

Topics: Adolescent; Adult; Drugs, Chinese Herbal; Evoked Potentials, Visual; Female; Humans; Male; Optic Atrophy, Hereditary, Leber; Phytotherapy; Ubiquinone; Visual Acuity; Young Adult

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

Topics: DNA, Mitochondrial; Electron Transport Complex I; Humans; Mitochondria; Mutation; Optic Atrophy, Hereditary, Leber; Ubiquinone; Water

Topics: Antioxidants; DNA, Mitochondrial; Humans; Optic Atrophy, Hereditary, Leber; Ubiquinone

Topics: Antioxidants; Humans; Optic Atrophy, Hereditary, Leber; Ubiquinone

In this retrospective, interventional, longitudinal small case series, we looked at the visual effects of pharmacologic intervention with 4-aminopyridine (4-AP) in chronic Leber's Hereditary Optic Neuropathy (LHON) patients who are non-responders to idebenone. We illustrate, as examples, the visual progression of three LHON patients with 4-AP as add-on therapy to idebenone. Each patient had a different primary LHON mutation and was treated with idebenone within one year of onset. No response to idebenone at 300 mg orally three times a day ranged from less than one year to 2.5 years, and the addition of 4-AP at 10 mg orally two times a day ranged from 24 to 29 months. Outcome measures included best-corrected distance visual acuity, color vision, automated perimetry, the average retinal nerve fiber layer (RNFL) thickness, and the full-field photopic negative response (PhNR) amplitude. The 19-year-old man with the LHON mutation 11778A > G had no response to the addition of 4-AP to idebenone. The 27-year-old man with the LHON mutation 3460A > G experienced a significant response to 4-AP. Finally, the 40-year-old man with the LHON mutation 14484 T > C had a milder response. Although this case series was too small to demonstrate the efficacy of idebenone with add-on 4AP, it allowed us to consider a new hypothesis that neuronal activity generated from 4-AP can add more potential for visual recovery in LHON patients.

Topics: 4-Aminopyridine; Adult; DNA, Mitochondrial; Drug Therapy, Combination; Humans; Male; Nerve Net; Neurons; Optic Atrophy, Hereditary, Leber; Retrospective Studies; Ubiquinone; Young Adult

Biodegradable poly(lactic-co-glycolic acid) microspheres (PLGA MSs) are attractive delivery systems for site-specific maintained release of therapeutic active substances into the intravitreal chamber. The design, development, and characterization of idebenone-loaded PLGA microspheres by means of an oil-in-water emulsion/solvent evaporation method enabled the obtention of appropriate production yield, encapsulation efficiency and loading values. MSs revealed spherical shape, with a size range of 10-25 μm and a smooth and non-porous surface. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated no chemical interactions between idebenone and polymers. Solid-state nuclear magnetic resonance (NMR), X-ray diffractometry, differential scanning calorimetry (DSC) and thermogravimetry (TGA) analyses indicated that microencapsulation led to drug amorphization. In vitro release profiles were fitted to a biexponential kinetic profile. Idebenone-loaded PLGA MSs showed no cytotoxic effects in an organotypic tissue model. Results suggest that PLGA MSs could be an alternative intraocular system for long-term idebenone administration, showing potential therapeutic advantages as a new therapeutic approach to the Leber's Hereditary Optic Neuropathy (LHON) treatment by intravitreal administration.

Topics: Humans; Microspheres; Optic Atrophy, Hereditary, Leber; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Ubiquinone

Leber's Hereditary Optic Neuropathy (LHON) is a hereditary mitochondrial neurodegenerative disease of unclear etiology and lack of available therapeutic alternatives. The main goal of the current pilot study was based on the evaluation of the feasibility and characteristics of prolonged and controlled idebenone release from a PCL intravitreal implant. The design, development, and characterization of idebenone-loaded PCL implants prepared by an homogenization/extrusion/solvent evaporation method allowed the obtention of high PY, EE and LC values. In vitro characterization was completed by the assessment of mechanical and instrumental properties. The in vitro release of idebenone from the PCL implants was assessed and the implant erosion was monitored by the mass loss and surface morphology changes. DSC was used to estimate stability and interaction among implant's components. The present work demonstrated the controlled and prolonged idebenone delivery from the PCL implants in an in vitro model. A consistent preclinical base was established, supporting the idea of idebenone-loaded PCL implants as a new strategy of long-term sustained intraocular delivery for the LHON treatment.

Topics: Animals; Chemistry, Pharmaceutical; Chickens; Chorioallantoic Membrane; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Implants; Drug Stability; Optic Atrophy, Hereditary, Leber; Pilot Projects; Polyesters; Ubiquinone

Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients.. Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939.. Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout.. Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%).. Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.

Topics: Humans; Japan; Male; Optic Atrophy, Hereditary, Leber; Prospective Studies; Ubiquinone; Visual Acuity

In September 2015, the first and so far only medication for treatment of Leber's hereditary optic neuropathy (LHON) was approved in the EU. The drug in question is idebenone (©Raxone) and has been given to all newly diagnosed patients of the University Eye Hospital Tuebingen since the approval of the drug. The aim of the study was to find out whether regular administration of the drug led to an improvement in vision. We retrospectively examined 2 cohorts of consecutive patients with newly occurred visual impairment and LHON diagnosis: One with the initial diagnosis made from January 2010 until April 2014 and a second from October 2015 until January 2020.. Retrospective, observational cohort study. All electronic medical files of newly diagnosed and genetically confirmed LHON patients of the University Eye Hospital Tuebingen from January 2010 until April 2014 (cohort 1) and October 2015 until January 2020 (cohort 2) with at least 12 months of follow-up examinations have been analyzed.. Five patients were included in the first and 7 patients in the second cohort. Patients of cohort 1 received no medication; patients of cohort 2, a daily dose of 900 mg idebenone. The primary visual acuity (VA) ranged between 0.03 and 0.5 in cohort 1 and did not improve during the observation period (median 60 months, range 23-87 months). The patients of cohort 2 have been observed for a median of 23 months (range 12-35 m). The primary VA ranged from 0.01 to 0.16. A recovery in one or both eyes with a final VA from 0.8 to 1.0 was experienced in 3 out of 7 patients. All patients showing a recovery of VA carried the m.11778G>A mutation.. The observed improvement in the treated cohort may be considered as a hint on the efficacy of idebenone in LHON. The time course of improvement suggests that idebenone should be given 1.5 years in newly diagnosed LHON cases.

Topics: DNA, Mitochondrial; Humans; Mutation; Optic Atrophy, Hereditary, Leber; Retrospective Studies; Ubiquinone

Topics: Humans; Japan; Optic Atrophy, Hereditary, Leber; Prospective Studies; Ubiquinone

Leber's hereditary optic neuropathy (LHON) is a rare inherited blindness caused by mutations in the mitochondrial DNA (mtDNA). The disorder is untreatable and tricky, as the existing chemotherapeutic agent Idebenone alleviates symptoms rather than overcoming the underlying cause. Although some studies have made progress on allotopic expression for LHON, in situ mitochondrial gene therapy remains challenging, which may simplify delivery procedures to be a promising therapeutic for LHON. LHON becomes more difficult to manage in the changed mitochondrial microenvironment, including increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP). Herein, a pathologically responsive mitochondrial gene delivery vector named [triphenylphosphine-terminated poly(sulfur-containing thioketal undecafluorohexylamine histamine) and Ide-terminated poly(sulfur-containing thioketal undecafluorohexylamine histamine)] (TISUH) is reported to facilitate commendable in situ mitochondrial gene therapy for LHON. TISUH directly targets diseased mitochondria via triphenylphosphine and fluorination addressing the decreasing MMP. In addition, TISUH can be disassembled by high mitochondrial ROS levels to release functional genes for enhancing gene transfection efficiency and fundamentally correcting genetic abnormalities. In both traditional and gene-mutation-induced LHON mouse models, TISUH-mediated gene therapy shows satisfactory curative effect through the sustained therapeutic protein expression in vivo. This work proposes a novel pathologically responsive in situ mitochondrial delivery platform and provides a promising approach for refractory LHON as well as other mtDNA mutated diseases treatments.

Topics: Animals; Disease Models, Animal; DNA; DNA, Mitochondrial; Electron Transport Complex I; Fluorescent Dyes; Genetic Therapy; Humans; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Mitochondria; Optic Atrophy, Hereditary, Leber; Polymers; Protein Subunits; Reactive Oxygen Species; Ubiquinone

Topics: DNA, Mitochondrial; Humans; Optic Atrophy, Hereditary, Leber; Ubiquinone

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by a subacute and progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In most cases, it results in optic nerve atrophy and permanently reduced visual acuity (VA). Idebenone has recently been approved in Europe for treating LHON. However, published clinical data has only focused on efficacy in patients within the first years after disease onset. The present study is the first to evaluate possible effects of idebenone treatment in patients with LHON when initiated after more than 5 years from disease onset.. Oral treatment with idebenone 300 mg tid was started in seven patients 5 to 51 years after LHON onset. All patients had genetically confirmed primary LHON mutations (m11778G>A, m14484T>C, and m13051G>A). Visual function of all fourteen eyes was tested every 3 months using logarithmic reading charts and automated static threshold perimetry. The obtained clinical data were analyzed retrospectively using a multivariate analysis for VA and the Wilcoxon signed-rank test for visual field data.. Before treatment, VA was 0.78 ± 0.38 logMAR (range 0.24 to 1.50 logMAR). During the first year of therapy, VA improved significantly by an average of - 0.20 ± 0.10 logMAR or 10 ± 5 ETDRS letters (P = 0.002; VA range 0.06 to 1.30 logMAR). Seven of fourteen eyes showed an improvement of 2 or more lines. Visual field mean deviation increased from - 8.02 ± 6.11 to - 6.48 ± 5.26 dB after 12 months, but this change was not statistically significant (P = 0.056).. The increase in VA of patients who have had LHON for more than 5 years observed soon after start of treatment may not constitute a coincidental spontaneous recovery. We hypothesize that the treatment response in chronic LHON was the result of a reactivated signal transduction in surviving dysfunctional RGCs. The results of this study indicate a beneficial effect of idebenone on improvement of visual function in LHON patients with established optic atrophy.

Topics: Adult; Aged; Antioxidants; Chronic Disease; Follow-Up Studies; Forecasting; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Retinal Ganglion Cells; Retrospective Studies; Tomography, Optical Coherence; Treatment Outcome; Ubiquinone; Visual Acuity; Visual Fields; Young Adult

Leber's Hereditary Optic Neuropathy (LHON) causes a rapid and severe decrease in visual acuity. Raxone. Retrospective study of the efficacy of Raxone. Seventeen patients, three women and 14 men, mean age 34.2 years, naive to treatment with Raxone. The results confirm the trend of Raxone

Topics: Adolescent; Adult; Disease Progression; Female; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Paris; Retrospective Studies; Treatment Outcome; Ubiquinone; Visual Acuity; Young Adult

Topics: Administration, Oral; Child, Preschool; Citrulline; DNA, Mitochondrial; Humans; Magnetic Resonance Imaging; Male; Mitochondrial Diseases; Mutation; Optic Atrophy, Hereditary, Leber; Tomography, Optical Coherence; Ubiquinone; Visual Acuity

Topics: Consensus; DNA, Mitochondrial; Humans; Optic Atrophy, Hereditary, Leber; Point Mutation; Ubiquinone

The diagnosis of acute optic neuropathy is made clinically. In young patients demyelinating optic neuritis is the most common cause. However, other autoimmune diseases, infections and other non-inflammatory conditions may also cause inflammation. Careful clinical workup is necessary to establish the correct diagnosis and treatment. We describe the clinical approach to a case of acute optic neuropathy with several atypical features. The same case was published in the Journal of Neuro-Ophthalmology.. A male teenager developed acute and painless bilateral visual loss. Fundoscopy revealed optic disc hypaeremia with telangiectasia. Magnetic resonance imaging demonstrated contrast enhancement of the optic nerves and chiasm without evidence of demyelinating disease. There was no visual improvement after methylprednisolone treatment. Genetic analysis for the 3 common Leber hereditary optic neuropathy (LHON) mutations was negative. However, idebenone treatment was followed by a marked improvement in visual function. Whole mitochondrial genome sequencing eventually detected a rare LHON mutation.. There are many different causes of acute optic neuropathy. Making the correct diagnosis is important, as clinical management differs. Idebenone is now a treatment option for LHON. Whole mitochondrial genome sequencing is sometimes necessary to confirm the diagnosis.

Topics: Adolescent; Antioxidants; Humans; Male; Ophthalmoscopy; Optic Atrophy, Hereditary, Leber; Point Mutation; Treatment Outcome; Ubiquinone; Vision Disorders; Visual Field Tests

A 28-year-old Caucasian man developed sudden painless vision loss in the right eye. He was diagnosed with optic neuritis. MRI showed white matter lesions consistent with multiple sclerosis (MS), but no optic nerve enhancement. Eight months later, the left eye was affected in the same manner. Examination showed right optic atrophy and apparent left optic disc swelling. Workup revealed positive Lyme IgG. Differential diagnosis included optic neuritis and Lyme optic neuropathy, and he was treated with intravenous steroids, intravenous immunoglobulin, plasmapheresis and intravenous ceftriaxone without improvement. Neuro-ophthalmology consultation led to identification of pseudo-optic disc oedema, and Leber's hereditary optic neuropathy (LHON) was suspected and confirmed by genetic testing. LHON may occur in association with MS, and should be considered in patients with MS with vision loss atypical for optic neuritis. This is especially important as new treatments for LHON (including gene therapy) are currently undergoing clinical trials.

Topics: Adult; Antioxidants; Diagnosis, Differential; Diagnostic Errors; Humans; Lyme Disease; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Optic Atrophy, Hereditary, Leber; Optic Neuritis; Ubiquinone; Vision, Low; White Matter

Topics: Aged; Female; Humans; Intraocular Pressure; Late Onset Disorders; Optic Atrophy, Hereditary, Leber; Pedigree; Tomography, Optical Coherence; Ubiquinone; Vision Disorders; Visual Acuity; Vitamin B 12; Vitamin B 12 Deficiency

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

Topics: Antioxidants; Child; Humans; Male; Optic Atrophy, Hereditary, Leber; Ubiquinone; Vision, Low

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

Topics: Antioxidants; Congresses as Topic; Consensus; Disease Management; Humans; International Cooperation; Ophthalmology; Optic Atrophy, Hereditary, Leber; Societies, Medical; Ubiquinone

Patients with Leber hereditary optic neuropathy (LHON) have a progressive decrease of their visual acuity which can deteriorate to <0.1. Some patients can have a partial recovery of their vision in one or both eyes. One prognostic factor associated with a recovery of vision is an early-age onset. The purpose of this study was to determine other clinical factors that are predictive of a good visual recovery.. Sixty-one Japanese LHON patients, with the 11,778 mutation and a mean age of 23.1 ± 12.1 years at the onset, were studied. All patients were initially examined at an acute stage of LHON and were followed for 3 to 10 years. At 1 year after the onset, the lowest visual acuity was <0.1 in all eyes. We studied the following parameters of patients with/without a final visual acuity of ≥ 0.2: sex; heavy consumption of cigarettes and alcohol; taking idebenone; mean age at onset; mean lowest visual acuity; and distribution of the lowest and the final visual acuity.. Fifteen (24.6%) of the 61 patients or 25 (20.5%) of the 122 eyes had a recovery of their visual acuity to ≥ 0.2. The mean age at onset of these 15 patients with visual recovery to ≥ 0.2 was 17.5 ± 7.7 years, and that of the 46 patients without visual recovery to ≥ 0.2 was 25.0 ± 12.8 years (P = 0.02, Mann-Whitney U test). The mean lowest visual acuity of the 25 eyes with visual recovery ≥ 0.2 was 0.04, and that of the 97 eyes without visual recovery to ≥ 0.2 was 0.015 (P < 0.001, Mann-Whitney U test). Fifty percent (15/30) of the eyes whose lowest visual acuity was ≥ 0.04 during 1 year after the onset had a visual recovery to ≥ 0.2, while 11% (10/92) of the eyes whose the lowest visual acuity was ≤ 0.03 had a visual recovery to ≥ 0.2 (P < 0.001, χ. A final visual acuity of ≥ 0.2 was associated with a less severe reduction of the visual acuity at 1 year after the onset. Our findings can be used to predict the visual prognosis in LHON patients.

Topics: Adolescent; Adult; Age of Onset; Aged; Antioxidants; Ascorbic Acid; Child; DNA Mutational Analysis; DNA, Mitochondrial; Female; Follow-Up Studies; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Point Mutation; Polymerase Chain Reaction; Prognosis; Recovery of Function; Retrospective Studies; Riboflavin; Ubiquinone; Vision Disorders; Visual Acuity; Visual Field Tests; Vitamin B Complex; Young Adult

Topics: Antioxidants; Humans; Optic Atrophy, Hereditary, Leber; Treatment Outcome; Ubiquinone

Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness among young adults. In this study, we investigated the potential of four quinone analogues (CoQ

Topics: Adenosine Triphosphate; Adolescent; Antioxidants; Cells, Cultured; Energy Metabolism; Fibroblasts; Humans; Male; Middle Aged; Optic Atrophy, Hereditary, Leber; Quinones; Reactive Oxygen Species; Ubiquinone; Young Adult

Idebenone (Raxone(®)), a short-chain benzoquinone, is the only disease-specific drug approved to treat visual impairment in adolescents and adults with Leber's hereditary optic neuropathy (LHON), a rare genetic mitochondrial disease that causes rapid and progressive bilateral vision loss. The mechanism of action of idebenone involves its antioxidant properties and ability to act as a mitochondrial electron carrier. Idebenone overcomes mitochondrial complex I respiratory chain deficiency in patients with LHON by transferring electrons directly to mitochondrial complex III (by-passing complex I), thereby restoring cellular energy (ATP) production and re-activating inactive-but-viable retinal ganglion cells, which ultimately prevents further vision loss and promotes vision recovery. The approval of idebenone in the treatment of LHON was based on the overall data from a randomized clinical trial, a follow-up study and real-world data. Taken together, these studies provide convincing evidence that oral idebenone 900 mg/day for 24 weeks has persistent beneficial effects in preventing further vision impairment and promoting vision recovery in patients with LHON relative to the natural course of the disease. Therefore, idebenone is a valuable agent to treat visual impairment in adolescents and adults with LHON.

Topics: Antioxidants; Humans; Optic Atrophy, Hereditary, Leber; Randomized Controlled Trials as Topic; Ubiquinone

Topics: Adolescent; DNA, Mitochondrial; Humans; Male; Mutation; NADH Dehydrogenase; Optic Atrophy, Hereditary, Leber; Ubiquinone

We report a case of a young Chinese male presenting with sequential, painless, bilateral visual loss in Hong Kong. He was diagnosed to have Leber's hereditary optic neuropathy with genetic workup showing G11778A mutation with over 80% heteroplasmy. He was started on idebenone treatment 11 months after onset of the binocular disease. To our best knowledge, this is the first case of Leber's hereditary optic neuropathy treated with idebenone in Hong Kong. The recent evidence of the diagnosis and treatment of this devastating disease is reviewed.

Topics: Adolescent; Antioxidants; Diagnosis, Differential; Hong Kong; Humans; Male; Optic Atrophy, Hereditary, Leber; Ubiquinone; Visual Acuity

Topics: Child; DNA, Mitochondrial; Humans; Male; Micronutrients; Mitochondrial Diseases; Mutation; Optic Atrophy, Hereditary, Leber; Pedigree; Polymerase Chain Reaction; Siblings; Treatment Outcome; Ubiquinone; Visual Acuity; Visual Fields

Defects in complex I due to mutations in mitochondrial DNA are associated with clinical features ranging from single organ manifestation like Leber hereditary optic neuropathy (LHON) to multiorgan disorders like mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. Specific mutations cause overlap syndromes combining several phenotypes, but the mechanisms of their biochemical effects are largely unknown. The m.3376G>A transition leading to p.E24K substitution in ND1 with LHON/MELAS phenotype was modeled here in a homologous position (NuoH-E36K) in the Escherichia coli enzyme and it almost totally abolished complex I activity. The more conservative mutation NuoH-E36Q resulted in higher apparent K(m) for ubiquinone and diminished inhibitor sensitivity. A NuoH homolog of the m.3865A>G transition, which has been found concomitantly in the overlap syndrome patient with the m.3376G>A, had only a minor effect. Consequences of a primary LHON-mutation m.3460G>A affecting the same extramembrane loop as the m.3376G>A substitution were also studied in the E. coli model and were found to be mild. The results indicate that the overlap syndrome-associated m.3376G>A transition in MTND1 is the pathogenic mutation and m.3865A>G transition has minor, if any, effect on presentation of the disease. The kinetic effects of the NuoH-E36Q mutation suggest its proximity to the putative ubiquinone binding domain in 49kD/PSST subunits. In all, m.3376G>A perturbs ubiquinone binding, a phenomenon found in LHON, and decreases the activity of fully assembled complex I as in MELAS.

Topics: Amino Acid Sequence; Animals; Electron Transport Complex I; Escherichia coli Proteins; Humans; MELAS Syndrome; Membrane Proteins; Mitochondria; Models, Biological; Molecular Sequence Data; Mutagenesis, Site-Directed; Mutation; NADH Dehydrogenase; Optic Atrophy, Hereditary, Leber; Protein Binding; Protein Subunits; Sequence Homology, Amino Acid; Ubiquinone

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.

Topics: Adult; Anesthetics, Intravenous; Humans; Infusions, Intravenous; Male; Muscle, Skeletal; Optic Atrophy, Hereditary, Leber; Oxidative Phosphorylation; Propofol; Risk Factors; Syndrome; Ubiquinone

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

Leber's hereditary optic neuropathy (LHON) is an inherited disease caused by mutations in complex I of the mitochondrial respiratory chain. The disease is characterized by loss of central vision due to retinal ganglion cell (RGC) dysfunction and optic nerve atrophy. Despite progress towards a better understanding of the disease, no therapeutic treatment is currently approved for this devastating disease. Idebenone, a short-chain benzoquinone, has shown promising evidence of efficacy in protecting vision loss and in accelerating recovery of visual acuity in patients with LHON. It was therefore of interest to study suitable LHON models in vitro and in vivo to identify anatomical correlates for this protective activity. At nanomolar concentrations, idebenone protected the rodent RGC cell line RGC-5 against complex I dysfunction in vitro. Consistent with the reported dosing and observed effects in LHON patients, we describe that in mice, idebenone penetrated into the eye at concentrations equivalent to those which protected RGC-5 cells from complex I dysfunction in vitro. Consequently, we next investigated the protective effect of idebenone in a mouse model of LHON, whereby mitochondrial complex I dysfunction was caused by exposure to rotenone. In this model, idebenone protected against the loss of retinal ganglion cells, reduction in retinal thickness and gliosis. Furthermore, consistent with this protection of retinal integrity, idebenone restored the functional loss of vision in this disease model. These results support the pharmacological activity of idebenone and indicate that idebenone holds potential as an effective treatment for vision loss in LHON patients.

Topics: Administration, Oral; Animals; Antioxidants; Cell Line; Cell Survival; Disease Models, Animal; Drug Administration Schedule; Electron Transport Complex I; Humans; Intravitreal Injections; Male; Mice; Mitochondria; Mutation; Optic Atrophy, Hereditary, Leber; Retinal Ganglion Cells; Rotenone; Ubiquinone; Visual Acuity

In this report, we describe a Taiwanese (Han Chinese) family with Leber's hereditary optic neuropathy. The family carried a mitochondrial DNA mutation (mtDNA m.14484T>C) associated with spontaneous visual improvement. A 15-year-old boy from this family was diagnosed with Leber's hereditary optic neuropathy 6 months after losing his vision. His vision recovered after 8 months of supportive treatment. His mother, older brother, and two sisters also had the same mutation and had previously experienced vision loss. In this family, there was no male predominance.

Topics: Adolescent; DNA, Mitochondrial; Female; Humans; Male; Optic Atrophy, Hereditary, Leber; Pedigree; Pentoxifylline; Point Mutation; Taiwan; Treatment Outcome; Ubiquinone; Vision, Ocular

Topics: Burkholderia; Canada; Giant Cell Arteritis; Humans; Multiple Sclerosis; Neurology; Ophthalmology; Optic Atrophy, Hereditary, Leber; Pseudotumor Cerebri; Retinal Artery Occlusion; Societies, Medical; Tissue Plasminogen Activator; Tomography, Optical Coherence; Ubiquinone

Topics: Antioxidants; Female; Humans; Male; Optic Atrophy, Hereditary, Leber; Placebos; Ubiquinone

Topics: Antioxidants; Female; Humans; Male; Optic Atrophy, Hereditary, Leber; Placebos; Ubiquinone

LHON (Leber hereditary optic neuropathy) is a maternally inherited disease that leads to sudden loss of central vision at a young age. There are three common primary LHON mutations, occurring at positions 3460, 11778 and 14484 in the human mtDNA (mitochondrial DNA), leading to amino acid substitutions in mitochondrial complex I subunits ND1, ND4 and ND6 respectively. We have now examined the effects of ND6 mutations on the function of complex I using the homologous NuoJ subunit of Escherichia coli NDH-1 (NADH:quinone oxidoreductase) as a model system. The assembly level of the NDH-1 mutants was assessed using electron transfer from deamino-NADH to the 'shortcut' electron acceptor HAR (hexammine ruthenium), whereas ubiquinone reductase activity was determined using DB (decylubiquinone) as a substrate. Mutant growth in minimal medium with malate as the main carbon source was used for initial screening of the efficiency of energy conservation by NDH-1. The results indicated that NuoJ-M64V, the equivalent of the common LHON mutation in ND6, had a mild effect on E. coli NDH-1 activity, while nearby mutations, particularly NuoJ-Y59F, NuoJ-V65G and NuoJ-M72V, severely impaired the DB reduction rate and cell growth on malate. NuoJ-Met64 and NuoJ-Met72 position mutants lowered the affinity of NDH-1 for DB and explicit C-type inhibitors, whereas NuoJ-Y59C displayed substrate inhibition by oxidized DB. The results are compatible with the notion that the ND6 subunit delineates the binding cavity of ubiquinone substrate, but does not directly take part in the catalytic reaction. How these changes in the enzyme's catalytic properties contribute to LHON pathogenesis is discussed.

Topics: Bacteria; Catalysis; DNA, Mitochondrial; Electron Transport Complex I; Escherichia coli; Female; Humans; Inhibitory Concentration 50; Kinetics; Male; Mitochondria; Mutagenesis; Mutation; Optic Atrophy, Hereditary, Leber; Ubiquinone

To ascertain the efficacy of idebenone and multivitamin treatment in Leber's hereditary optic neuropathy (LHON).. Two patients diagnosed of unilateral LHON were treated with megadoses of idebenone, vitamin C and riboflavin for one year. They were examined clinically before, during and after treatment.. No improvement of visual function was observed. Despite the idebenone treatment, in both cases the second eye became involved.. Despite previous reports of visual recovery with idebenone in patients with LHON, our experience shows that an effective treatment for Leber's disease remains to be found.

Topics: Adult; Antioxidants; Ascorbic Acid; Benzoquinones; Female; Humans; Male; Optic Atrophy, Hereditary, Leber; Riboflavin; Treatment Failure; Ubiquinone; Vitamin B Complex; Vitamins

Topics: Adult; Antioxidants; Coenzymes; DNA Mutational Analysis; DNA, Mitochondrial; Humans; Male; Optic Atrophy, Hereditary, Leber; Point Mutation; Ubiquinone; Vision Disorders; Visual Acuity

The previously unrecognised association of myoclonus in two patients with LHON with the 11778/ND4 pathogenic mutation is described. EEG failed to disclose epileptic figures, and a back averaging study suggested that myoclonus was cortical in origin in both patients.

Topics: Adult; Anti-Inflammatory Agents; Antioxidants; Benzoquinones; Biopsy; Disease Progression; Electroencephalography; Electromyography; Evoked Potentials, Visual; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Myoclonus; Optic Atrophy, Hereditary, Leber; Steroids; Treatment Outcome; Ubiquinone; Visual Acuity