Evidence map›Paper›PMID 40879302›Full record

ArticleHuman molecular genetics2025

Combination treatment with antioxidants and creatine alleviates common and variant-specific mitochondrial impairments in Leber's hereditary optic neuropathy patient-derived fibroblasts.

Donald Xhuti, Alessandra Chiarot, Mahek Minhas, Samantha Tobia, Nicoletta de Maat, Katherine Manta, Sean Y Ng, Mark A Tarnopolsky, Joshua P Nederveen

Abstract read
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In one paragraph

Article in Human molecular genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Donald XhutiDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Alessandra ChiarotDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Mahek MinhasDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Samantha TobiaDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Nicoletta de MaatDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Katherine MantaDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Sean Y NgDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Mark A TarnopolskyDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.
Joshua P NederveenDepartment of Pediatrics, McMaster University Medical Centre, 1200 Main Street West, Hamilton, ON L8S 3Z5, Canada.ORCID 0000-0002-9290-5602

Funding

CIHR 143325MitoCanadaMuscular Dystrophy Canada Research FellowshipNatural Sciences and Engineering Research Council of Canada Student ResearchNeuromuscular Disease Network for Canada
6 · The paper itself

Abstract

Leber's hereditary optic neuropathy (LHON) is characterized by painless and rapidly progressive central vision loss, caused by various mutations in mitochondrial DNA, leading to a high genetic and phenotypic heterogeneity. Currently, the only approved therapy is idebenone, a CoQ10 synthetic analogue, that improved visual acuity in some LHON patients; however, results are highly variable due its dependency on functional NAD(P)H oxidoreductase I (NQO1) protein levels, thus limiting broader applicability. Targeting the biochemical respiratory chain defect and mitigating reactive oxygen species emission using alternative treatments which act independent of NQO1 protein content, represent a promising therapeutic strategy for all LHON patients. Here, we first characterized mitochondrial biology of three distinct LHON mutations in patient-derived fibroblasts and evaluated the effects of a nutraceutical combination treatment in addressing these shared pathophysiological mechanisms. We identified a range of mitochondrial characteristics common among various LHON mutations, including higher ROS levels, altered autophagy programming, and reduced mitochondrial bioenergetics. Repeated antioxidant and creatine-based treatment (ACT) conferred a favorable stress-resistant phenotype in LHON cells, which was similar to, and in some cases superior to, the effects observed with idebenone treatment, irrespective of NQO1 protein expression. This phenotype was associated with enhanced mitochondrial biology, as evidenced by reduced reactive oxygen species levels, increased cellular respiration, and correction of autophagic flux. Overall, our findings reveal both common and divergent mitochondrial phenotypes among LHON-related mutations and highlight the potential of accessible multi-ingredient nutraceutical interventions that could benefit all LHON patients.

Indexed as

AntioxidantsCreatineMitochondriaOptic Atrophy, Hereditary, LeberDNA, MitochondrialFibroblastsHumansMutationNAD(P)H Dehydrogenase (Quinone)Reactive Oxygen SpeciesUbiquinoneAntioxidantsCreatineDNA, MitochondrialidebenoneNAD(P)H Dehydrogenase (Quinone)NQO1 protein, humanReactive Oxygen SpeciesUbiquinoneAntioxidantAutophagyCreatineLeber hereditary optic neuropathyMitochondria

Identifiers

PMID40879302
PMCPMC12529665

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