ArticleInvestigative ophthalmology & visual science2014
LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: biodistribution and toxicology profile.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 38 papers, 2 of them syntheses that pooled it.
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
An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (scAAV2-P1ND4v2) for Gene Therapy of Leber's Hereditary Optic Neuropathy (LHON) Caused by the G11778A Mutation in Mitochondrial DNA
Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Leber's Hereditary Optic Neuropathy as a Promising Disease for Gene Therapy Development.Advances in therapy · 2019Pooled it
- Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy.Brain : a journal of neurology · 2023Trial
- Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy.Scientific reports · 2016Trial
- ELP1 gene augmentation restores visual function in a mouse model of familial dysautonomia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in familial dysautonomia.Molecular therapy. Nucleic acids · 2026Article
- Oxidative stress imbalance and cellular damage mediated by the ND4 G11778A mutation.Scientific reports · 2026Article
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Development of a cell-penetrating peptide-based nanocomplex for long-term delivery of intact mitochondrial DNA into epithelial cells.Molecular therapy. Nucleic acids · 2025Article
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Technological advances in the diagnosis and management of inherited optic neuropathies.Frontiers in neurology · 2025Review
- Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators.Scientific reports · 2023Article
- Clinical Approaches for Mitochondrial Diseases.Cells · 2023Review
- Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder.Journal of clinical medicine · 2023Review
- Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model.Frontiers in neuroscience · 2023Article
- Neuroprotection and Neuroregeneration Strategies Using the rNAION Model: Theory, Histology, Problems, Results and Analytical Approaches.International journal of molecular sciences · 2022Article
- From Bench to Bedside-Delivering Gene Therapy for Leber Hereditary Optic Neuropathy.Cold Spring Harbor perspectives in medicine · 2022Review
- Absence of lenadogene nolparvovec DNA in a brain tumor biopsy from a patient in the REVERSE clinical study, a case report.BMC neurology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
purposeTo demonstrate safety and efficacy of allotopic human ND4 for treatment of a Leber's hereditary optic neuropathy (LHON) mouse model harboring the G11778A mitochondrial mutation.
methodsWe induced LHON in mice by intravitreal injection of mutant (G11778A) human ND4 DNA, responsible for most cases of LHON, that was directed to mitochondria using an AAV2 vector to which we appended a mitochondrial targeting sequence to the VP2 capsid. We then attempted rescue of visual loss using our test article (ScAAV2-P1ND4v2) containing a synthetic nuclear encoded G11778G ND4 gene that was allotopically expressed. Control mice either were uninjected or received AAV2-GFP or AAV2-mCherry. We performed RT-PCR and confocal microscopy at 2 weeks post injection. Pattern electroretinograms (PERGs), spectral-domain optical coherence tomography (SD-OCT), histology, and transmission electron microscopy (TEM) were performed. For toxicology and biodistribution studies, the test article was administered intravitreally to rats and rhesus macaques at different doses.
resultsMutant and wild-type ND4 were efficiently expressed in the mitochondria of retinal ganglion cells (RGCs). Visual function assessed by serial PERGs and retinal structure by serial SD-OCT showed a significant rescue by the test article. Histology and ultrastructural analysis confirmed that loss of RGCs and demise of axons was prevented by ScAAV2-P1ND4v2. Rat and nonhuman primate biodistribution studies showed that vector spread outside the injected eye into spleen and lymph nodes was minimal. Histopathology of tissues and organs including the eyes was comparable to that of uninfected and saline-injected eyes.
conclusionsAllotopically expressed wild-type ND4 prevents the phenotype induced by G11778A mitochondrial DNA with a toxicology profile acceptable for testing in a phase I clinical trial.
Indexed as
Identifiers
What OpenQuestion holds
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.