ArticleAmerican journal of human genetics2008
Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction.
Article in American journal of human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01267422 (Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy), which is not on this map. Cited by 100 papers.
What it found
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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.
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.
Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy
Who cites it
100 citing papers in PubMed, 219 citations in OpenAlex.
- Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.Scientific reports · 2016Trial
- Leber hereditary optic neuropathy gene therapy clinical trial recruitment: year 1.Archives of ophthalmology (Chicago, Ill. : 1960) · 2010Trial
- Culture of Human Retinal Explants as an Ex Vivo Model for Retinal Gene Therapy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Development of Two In Vitro ND1-LHON Models for Evaluating Gene Therapy Efficacy.Investigative ophthalmology & visual science · 2025Article
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Rodent Models of Retinal Degeneration: From Purified Cells in Culture to Living Animals.Cold Spring Harbor perspectives in medicine · 2024Review
- HOXC11-mediated regulation of mitochondrial function modulates chemoresistance in colorectal cancer.BMC cancer · 2024Article
- Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells.Journal of molecular cell biology · 2024Article
- Current and Future Landscape in Genetic Therapies for Leber Hereditary Optic Neuropathy.Cells · 2023Review
- Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation.Journal of biomedical science · 2023Article
- Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation.Ophthalmology and therapy · 2023Article
- Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder.Journal of clinical medicine · 2023Review
- AAV for Gene Therapy in Ocular Diseases: Progress and Prospects.Research (Washington, D.C.) · 2023Review
- Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model.Frontiers in neuroscience · 2023Article
- Current advances in gene therapy of mitochondrial diseases.Journal of translational medicine · 2022Review
- Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing.Innovation (Cambridge (Mass.)) · 2022Article
- Phenotypic Variation of Autosomal Recessive Leber Hereditary Optic Neuropathy (arLHON) in One Family.Diagnostics (Basel, Switzerland) · 2022Article
- Leber Hereditary Optic Neuropathy: Molecular Pathophysiology and Updates on Gene Therapy.Biomedicines · 2022Review
- Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective.Pharmaceutics · 2022Review
- Cloning and Organelle Expression of Bamboo Mitochondrial Complex I Subunits Nad1, Nad2, Nad4, and Nad5 in the YeastInternational journal of molecular sciences · 2022Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial diseases due to mutations in mitochondrial DNA can no longer be ignored in most medical areas. With prevalence certainly higher than one in 6000, they probably represent the most common form of metabolic disorders. Despite progress in identification of their molecular mechanisms, little has been done with regard to therapy. We have recently optimized the allotopic expression for the mitochondrial genes ATP6, ND1, and ND4 and obtained a complete and long-lasting rescue of mitochondrial dysfunction in the human fibroblasts in which these genes were mutated. However, biosafety and benefit to mitochondrial function must be validated in animal models prior to clinical applications. To create an animal model of Leber Hereditary Optic Neuropathy (LHON), we introduced the human ND4 gene harboring the G11778A mutation, responsible of 60% of LHON cases, to rat eyes by in vivo electroporation. The treatment induced the degeneration of retinal ganglion cells (RGCs), which were 40% less abundant in treated eyes than in control eyes. This deleterious effect was also confirmed in primary cell culture, in which both RGC survival and neurite outgrowth were compromised. Importantly, RGC loss was clearly associated with a decline in visual performance. A subsequent electroporation with wild-type ND4 prevented both RGC loss and the impairment of visual function. Hence, these data provide the proof-of-principle that optimized allotopic expression can be an effective treatment for LHON, and they open the way to clinical studies on other devastating mitochondrial disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.