Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy

Abstract

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to optic atrophy due to degeneration of the retinal ganglion cell. A curative treatment is not available at the moment, but a new antioxidant drug, Idebenone, is expected to reduce the progression of the disorder. Two male patients, genetically confirmed with LHON, were clinically, morphologically, and electrophysiologically evaluated, before and three, six, nine and 12 months after starting the treatment. The patient with 3460G>A mutation in mitochondrially-encoded nicotinamide adenine dinucleotide, reduced form (NADH):ubiquinone oxidoreductase core subunit (mtND)1 gene showed an improvement in visual acuity, visual field, and visual evoked potentials with no effect on morphological examinations, while the patient with 11778G>A mutation in mtND4 gene showed no functional, nor morphological recovery after one year of treatment. This study demonstrates that Idebenone, depending on the genetic profile of the disease, may be effective in functional improvement in patients with LHON.

Apparent Opportunities and Hidden Pitfalls: The Conflicting Results of Restoring NRF2-Regulated Redox Metabolism in Friedreich’s Ataxia Pre-Clinical Models and Clinical Trials

“…In vitro, IDE, displays vigorous antioxidant activity by facilitating electrons flux through the mitochondrial electron transport chain, thus leading to increased production of ATP [205,206]. Therefore, IDE has been used in mitochondria-related diseases such as Leber hereditary optic neuropathy (LHON) [207,208] and for the treatment of hereditary myopathies [209]. IDE was shown to activate the NRF2 signalling pathway by promoting its nuclear translocation after H 2 O 2 treatment by using an in vitro model of a human retinal pigment epithelium (RPE) cell line [210].…”

Letter to the Editor: Variable response to Idebenone in LHON is multifactorial

“…We read with interest the article by Mercuţ et al about two patients with Leber's hereditary optic neuropathy (LHON), a 15-year-old male carrying the mitochondrial deoxyribonucleic acid (mtDNA) m.3460G>A variant in MT-ND1 [patient (1)] and an 11-year-old male carrying the m.11778G>A variant in MT-ND4 [patient (2)], in whom the morphological and functional response to Idebenone treatment was monitored in three months intervals over a period of one year [1]. Patient (1) experienced improvement of visual acuity, visual fields defects, and visually evoked potentials (VEPs) but no improvement was found regarding the retinal abnormalities, while patient (2) experienced neither functional nor morphological improvement of his abnormalities [1]. The study is appealing but raises concerns that should be discussed.…”

“…The study is appealing but raises concerns that should be discussed. A limitation of the study is that heteroplasmy rates of the causative mtDNA variants were not provided [ 1 ]. Knowing heteroplasmy rates is crucial as they may contribute to the phenotypic expression of mtDNA variants and could be responsible for the variable treatment responses of the two index patients.…”

Letter to the Editor: Retinal morphological and functional response to Idebenone therapy in Leber hereditary optic neuropathy

“…

We read with interest the letter [1] from Josef Finsterer & Sounira Mehri about our article regarding the morphological and functional response to Idebenone therapy in patients with Leber hereditary optic neuropathy (LHON), where two pediatric patients, genetically confirmed, were periodically followed-up over a period of one year after we initiated the treatment [2]. We thank them for the interest shown in this topic and we want to answer the questions they have formulated regarding our study.The first concern was the fact that the heteroplasmy rates of the causative mitochondrial deoxyribonucleic acid (mtDNA) were not provided in our study.

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