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

Detalhes bibliográficos
Autor(a) principal: Catarino,Claudia B.
Data de Publicação: 2017
Outros Autores: Klopstock,Thomas
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Journal of Inborn Errors of Metabolism and Screening
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942017000100707
Resumo: Abstract 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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spelling Use of Idebenone for the Treatment of Leber’s Hereditary Optic NeuropathyLHONcomplex Irespiratory chainoxidative phosphorylationLeber’s hereditary optic neuropathyLeber optic atrophyLeber diseaseidebenone, mitochondrial diseaseAbstract 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.Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT)2017-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942017000100707Journal of Inborn Errors of Metabolism and Screening v.5 2017reponame:Journal of Inborn Errors of Metabolism and Screeninginstname:Instituto Genética para Todos (IGPT)instacron:IGPT10.1177/2326409817731112info:eu-repo/semantics/openAccessCatarino,Claudia B.Klopstock,Thomaseng2019-05-14T00:00:00Zoai:scielo:S2326-45942017000100707Revistahttp://jiems-journal.org/ONGhttps://old.scielo.br/oai/scielo-oai.phpjiems@jiems-journal.org||rgiugliani@hcpa.edu.br2326-45942326-4594opendoar:2019-05-14T00:00Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT)false
dc.title.none.fl_str_mv Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
title Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
spellingShingle Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
Catarino,Claudia B.
LHON
complex I
respiratory chain
oxidative phosphorylation
Leber’s hereditary optic neuropathy
Leber optic atrophy
Leber disease
idebenone, mitochondrial disease
title_short Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
title_full Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
title_fullStr Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
title_full_unstemmed Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
title_sort Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
author Catarino,Claudia B.
author_facet Catarino,Claudia B.
Klopstock,Thomas
author_role author
author2 Klopstock,Thomas
author2_role author
dc.contributor.author.fl_str_mv Catarino,Claudia B.
Klopstock,Thomas
dc.subject.por.fl_str_mv LHON
complex I
respiratory chain
oxidative phosphorylation
Leber’s hereditary optic neuropathy
Leber optic atrophy
Leber disease
idebenone, mitochondrial disease
topic LHON
complex I
respiratory chain
oxidative phosphorylation
Leber’s hereditary optic neuropathy
Leber optic atrophy
Leber disease
idebenone, mitochondrial disease
description Abstract 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-01-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
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dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942017000100707
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942017000100707
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1177/2326409817731112
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT)
publisher.none.fl_str_mv Latin American Society Inborn Errors and Neonatal Screening (SLEIMPN); Instituto Genética para Todos (IGPT)
dc.source.none.fl_str_mv Journal of Inborn Errors of Metabolism and Screening v.5 2017
reponame:Journal of Inborn Errors of Metabolism and Screening
instname:Instituto Genética para Todos (IGPT)
instacron:IGPT
instname_str Instituto Genética para Todos (IGPT)
instacron_str IGPT
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reponame_str Journal of Inborn Errors of Metabolism and Screening
collection Journal of Inborn Errors of Metabolism and Screening
repository.name.fl_str_mv Journal of Inborn Errors of Metabolism and Screening - Instituto Genética para Todos (IGPT)
repository.mail.fl_str_mv jiems@jiems-journal.org||rgiugliani@hcpa.edu.br
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