Novel use of idebenone in Leber’s hereditary optic neuropathy in Hong Kong

Cheng, SW; Ko, CH; Yau, SK; Mak, Chloe Miu; Yuen, Y K; Cy, Lee

doi:10.12809/hkmj134085

Cited by 8 publications

(4 citation statements)

References 14 publications

(10 reference statements)

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“…Idebenone (2,3‐dimethoxy‐5‐methyl‐6‐[10‐hydroxydecyl]‐1,4‐benzoquinonenoben) is a drug previously tested in clinical trials and already approved in some countries for the treatment of certain diseases associated with mitochondrial dysfunction , including Leber's hereditary optic neuropathy and Duchenne's muscular dystrophy. It is a synthetic quinone analog compound of coenzyme Q10 with a shorter aliphatic chain, and is considered a potent antioxidant that protects cells against enhanced ROS toxicity .…”

Section: Introductionmentioning

confidence: 99%

Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

Blanco

Pedersen

Wang

et al. 2020

Arthritis & Rheumatology

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Objective A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog and an antioxidant that has been used in humans to treat diverse diseases in which mitochondrial function is impaired. This study was undertaken to assess whether idebenone ameliorates lupus in murine models. Methods Idebenone was administered orally to MRL/lpr mice at 2 different doses (1 gm/kg or 1.5 gm/kg idebenone‐containing diet) for 8 weeks. At peak disease activity, clinical, immunologic, and metabolic parameters were analyzed and compared to those in untreated mice (n = 10 per treatment group). Results were confirmed in the lupus‐prone NZM2328 mouse model. Results In MRL/lpr mice, idebenone‐treated mice showed a significant reduction in mortality incidence (P < 0.01 versus untreated mice), and the treatment attenuated several disease features, including glomerular inflammation and fibrosis (each P < 0.05 versus untreated mice), and improved renal function in association with decreased renal expression of interleukin‐17A (IL‐17A) and mature IL‐18. Levels of splenic proinflammatory cytokines and inflammasome‐related genes were significantly decreased (at least P < 0.05 and some with higher significance) in mice treated with idebenone, while no obvious drug toxicity was observed. Idebenone inhibited neutrophil extracellular trap formation in neutrophils from lupus‐prone mice (P < 0.05) and human patients with SLE. Idebenone also improved mitochondrial metabolism (30% increase in basal respiration and ATP production), reduced the extent of heart lipid peroxidation (by one‐half that of untreated mice), and significantly improved endothelium‐dependent vasorelaxation (P < 0.001). NZM2328 mice exposed to idebenone also displayed improvements in renal and systemic inflammation, reducing the kidney pathology score (P < 0.05), IgG/C3 deposition (P < 0.05), and the gene expression of interferon, proinflammatory, and inflammasome‐related genes (at least P < 0.05 and some with higher significance). Conclusion Idebenone ameliorates murine lupus disease activity and the severity of organ damage, supporting the hypothesis that agents that modulate mitochondrial biologic processes may have a therapeutic role in human SLE.

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Section: Introductionmentioning

confidence: 99%

Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

Blanco

Pedersen

Wang

et al. 2020

Arthritis & Rheumatology

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“…LHON is a debilitating disease that significantly impacts patients and their families with no effective treatment available. Effectiveness of coenzyme Q10 [ 82 , 83 ] and idebenone in improving visual acuity of G11778A LHON patients shown in previous studies [ 44 , 61 , 84 ] was inconclusive. However, in recent years, the exploration of gene therapy for treating LHON patients has brought hope for LHON patients.…”

Section: Discussionmentioning

confidence: 99%

Leber’s Hereditary Optic Neuropathy with Mitochondrial DNA Mutation G11778A: A Systematic Literature Review and Meta‐Analysis

Yuan

Zhao²,

Pang³

et al. 2023

BioMed Research International

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Background. LHON is a progressive disease with early disease onset and male predominance, usually causing devastating visual loss to patients. These systematic review and meta-analysis are aimed at summarizing epidemiology, disease onset and progression, visual recovery, risk factors, and treatment options of Leber’s hereditary optic neuropathy (LHON) with mitochondrial DNA mutation G11778A from current evidence. Methods. The PubMed database was examined from its inception date to November 2021. Data from included studies were pooled with either a fixed-effects model or a random-effects model, depending on the results of heterogeneity tests. Sensitivity analysis was conducted to test the robustness of results. Results. A total of 41 articles were included in the systematic review for qualitative analysis, and 34 articles were included for quantitative meta-analysis. The pooled estimate of proportion of G11778A mutation among the three primary mutations of mitochondrial DNA (G11778A, G3460A, and T14484C) for LHON was 73% (95% CI: 67% and 79%), and the LHON patients with G11778A mutation included the pooled male ratio estimate of 77% (76% and 79%), the pooled age estimate of 35.3 years (33.2 years and 37.3 years), the pooled onset age estimate of 22.1 years (19.7 years and 24.6 years), the pooled visual acuity estimate of 1.4 LogMAR (1.2 LogMAR and 1.6 LogMAR), and the pooled estimate of spontaneous visual recovery rate (in either 1 eye) of 20% (15% and 27%). Conclusions. The G11778A mutation is a prevalent mitochondrial DNA mutation accounting for over half of LHON cases with three primary mutations. Spontaneous visual recovery is rare, and no effective treatment is currently available.

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“…The efficacy, safety and good tolerability of idebenone were documented, with only mild to moderate associated-side effects commonly reported ( Klopstock et al, 2011 ; 2013; Lyseng-Williamson, 2016 ). Clinical practice has also indicated a beneficial effect of idebenone on improving visual function ( Cheng et al, 2014 ), although once the disease has become chronic, the efficacy of idebenone is yet to be ascertained ( Pemp et al, 2019 ). This could explain the utilization profile ( Figure 3C ) that depends both on the phase of disease in which the diagnosis is made and on the poor efficacy of idebenone in end-stage LHON.…”

Section: Discussionmentioning

confidence: 99%

Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study

et al. 2022

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Background: Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data.Methods: A total of 21 orphan drugs used in outpatient settings, approved in the European Union before or during the 2008–2018 period and involving 15 rare diseases, were included in the study. The monitored population included patients with one of the conditions surveilled by the population-based Tuscany Registry of Rare Diseases and diagnosed between 2000–2018. A multi-database approach was applied, by linking data from the registry with information collected in drug prescriptions databases. The prevalence and intensity of use were estimated for the selected orphan drugs and other non-orphan medications, used to treat the same rare disease and for which a change in the prevalence of use was hypothesized after authorization of the orphan drug.Results: For some diseases (acquired aplastic anemia, tuberous sclerosis complex, most metabolic diseases) a low prevalence of orphan drugs use was observed (range between 1.1–12.5%). Conversely, orphan drugs were frequently used in hemophilia B, Wilson disease and idiopathic pulmonary fibrosis (maximum of 78.3, 47.6 and 41.8%, respectively). For hemophilia B and Leber’s hereditary optic neuropathy, there are currently no other medications used in clinical practice in addition to orphan drugs. Six orphan drugs were used for the treatment of pulmonary arterial hypertension, appearing the elective therapy for this disease, albeit with different utilization profiles (range of prevalence 1.7–55.6%).Conclusion: To the best of our knowledge, this is the first study investigating the utilization profile of orphan drugs prescribed in a defined geographical area, and providing relevant information to monitor over time potential changes in the prevalence of these medications as well as in the health care decision making.

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Novel use of idebenone in Leber’s hereditary optic neuropathy in Hong Kong

Cited by 8 publications

References 14 publications

Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone

Leber’s Hereditary Optic Neuropathy with Mitochondrial DNA Mutation G11778A: A Systematic Literature Review and Meta‐Analysis

Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study

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