Idebenone Treatment In Leber's Hereditary Optic Neuropathy

Carelli, Valerio; Morgia, Chiara La; Valentino, Maria Lucia; Rizzo, Giovanni; Carbonelli, Michele; Negri, Anna Maria De; Sadun, Federico; Carta, Arturo; Guerriero, Silvana; Simonelli, Francesca; Sadun, Alfredo A.; Aggarwal, Divya; Liguori, Rocco; Avoni, Patrizia; Baruzzi, Agostino; Zeviani, Massimo; Montagna, Pasquale; Barboni, Piero

doi:10.1093/brain/awr180

Cited by 205 publications

(162 citation statements)

References 8 publications

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“…Although this result should be considered with caution, it is compatible with previous clinical evidence of the partial efficacy of idebenone treatment in LHON. 26,27 However, the most interesting findings of the current study concern our results in OPA1-DOA, to our knowledge the first for this patient group based on DTI. We found widespread WM diffusivity changes without a clear prevalence in a specific pathway.…”

Section: Discussionmentioning

confidence: 52%

Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies

Manners¹,

Rizzo²,

Morgia

et al. 2015

American Journal of Neuroradiology

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BACKGROUND AND PURPOSE:Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features.

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Section: Discussionmentioning

confidence: 52%

Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies

Manners¹,

Rizzo²,

Morgia

et al. 2015

American Journal of Neuroradiology

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“…The proportion of patients or eyes with visual recovery, defined as gain of at least 2 lines on Snellen acuity or a change from "off-chart" to "on-chart," was higher for the group treated with idebenone compared to the untreated group. 22 Taken together, the data from the RHODOS study and from this retrospective study suggest that treatment with idebenone, when started early, increases the probability of visual recovery in LHON and may change the natural history of the disease. Table 2 summarizes these data.…”

mentioning

confidence: 65%

“…The therapy with idebenone is likely to have most impact when started early, 32 since retinal ganglion cell loss is still minimal in the early phase of disease. 22 Currently, there is no robust evidence to support the use of idebenone in patients with long-standing visual loss, and this warrants further research. 3.…”

Section: Ideal Duration Of Treatment a Longer Treatment Periodmentioning

confidence: 99%

“…22 The mean time to recovery was about 17 months after starting treatment with idebenone. 15,22 2. Maximum time window from symptom onset to starting treatment with idebenone.…”

Section: Ideal Duration Of Treatment a Longer Treatment Periodmentioning

confidence: 99%

“…This added to the evidence from case reports and small case series, reviewed in Table 1, [12][13][14][15][16][17][18][19][20][21] and one large retrospective open-label study. 22 With the sum of the available evidence, idebenone was approved in September 2015 in the European Union for the treatment of visual impairment in adolescent (12 years and older) and adult patients with LHON. 23,24 Recently, idebenone was also found in a phase III randomized clinical trial (RCT) to significantly reduce the loss of respiratory function in patients with Duchenne muscular dystrophy.…”

Section: Introductionmentioning

confidence: 99%

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Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy

Catarino

Klopstock

2017

Journal of Inborn Errors of Metabolism and Screening

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Leber's hereditary optic neuropathy (LHON) is one of the most frequent mitochondrial disorders. It is caused by mutations in genes of the mitochondrial DNA coding for subunits of the respiratory chain and leads to severe bilateral vision loss, from which spontaneous recovery is infrequent. Retinal ganglion cells show a selective vulnerability to mitochondrial dysfunction in LHON. Idebenone is the first medication approved for LHON. It is a short-chain benzoquinone, which is an analogue of coenzyme Q10, but with distinct properties and mechanisms of action. Idebenone is a potent antioxidant and inhibitor of lipid peroxidation. Importantly, it facilitates electron flux directly to complex III, bypassing the dysfunctional complex I of the mitochondrial respiratory chain, thereby increasing adenosine triphosphate (ATP) production. In the Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) randomized placebo-controlled clinical trial, 85 patients with LHON were enrolled, in the first 5 years after symptom onset, and randomized to either idebenone 900 mg/d for 6 months or placebo. Idebenone was well tolerated, and although the prespecified primary end point (best recovery in visual acuity [VA]) did not reach statistical significance, all secondary end points (change in best VA, change of VA of best eye at baseline, and change of VA in all eyes) showed a trend toward visual recovery in favor of idebenone. An increasing body of evidence shows that idebenone is effective and safe for the treatment of patients with LHON, including a large retrospective open-label study, several case reports and case series, an expanded access program, and ongoing post-authorization clinical studies. Here, we review the literature on idebenone for the treatment of patients with LHON.

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Effect of EPI-743 on the Clinical Course of the Mitochondrial Disease Leber Hereditary Optic Neuropathy

et al. 2012

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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. Design: Open-label clinical trial. Setting: 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). Main Outcome Measures: 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. Results: 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. Conclusions: 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.

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Idebenone Treatment In Leber's Hereditary Optic Neuropathy

Cited by 205 publications

References 8 publications

Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies

Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies

Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy

Effect of EPI-743 on the Clinical Course of the Mitochondrial Disease Leber Hereditary Optic Neuropathy

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