Use of Idebenone for the Treatment of Leber’s Hereditary Optic Neuropathy
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | |
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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Journal of Inborn Errors of Metabolism and Screening |
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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 |
status_str |
publishedVersion |
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 |
eu_rights_str_mv |
openAccess |
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 |
institution |
IGPT |
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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1754732519997046784 |