ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Long-term correction of very long-chain acyl-coA dehydrogenase deficiency in mice using AAV9 gene therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 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.
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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.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- From lipid function to dysfunction: Very long-chain fatty acids as emerging regulators of neuroinflammatory pathways.iScience · 2026Review
- Interleukin-10 expressing B lineage cells in visceral adipose tissue protect against aging-related insulin resistance and extend lifespan.Nature communications · 2026Article
- Restoration of Interaction Between Fatty Acid Oxidation and Electron Transport Chain Proteins In Vitro by Addition of Recombinant VLCAD.Biomedicines · 2026Article
- The crosstalk between mitochondrial dysfunction and fatty acid metabolism in heart failure: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2025Review
- The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients.Investigative ophthalmology & visual science · 2024Article
- A review of fatty acid oxidation disorder mouse models.Molecular genetics and metabolism · 2024Review
- Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome.Biomolecules · 2023Article
- Synthetic mRNA rescues very long-chain acyl-CoA dehydrogenase deficiency in patient fibroblasts and a murine model.Molecular genetics and metabolism · 2023Article
- Article
- Adipose Tissue: An Emerging Target for Adeno-associated Viral Vectors.Molecular therapy. Methods & clinical development · 2020Review
- AAV9 gene replacement therapy for respiratory insufficiency in very-long chain acyl-CoA dehydrogenase deficiency.Journal of inherited metabolic disease · 2019Article
- ITRAQ-Based Quantitative Proteomics Reveals the Proteome Profiles of Primary Duck Embryo Fibroblast Cells Infected with Duck Tembusu Virus.BioMed research international · 2019Article
- Lipid Myopathies.Journal of clinical medicine · 2018Review
- Gene Therapy 2017: Progress and Future Directions.Clinical and translational science · 2017Review
- Article
- Reprogramming adipose tissue-derived mesenchymal stem cells into pluripotent stem cells by a mutant adeno-associated viral vector.Human gene therapy methods · 2014Article
- Adeno-associated virus-mediated gene therapy for metabolic myopathy.Human gene therapy · 2013Review
- Cell and gene therapy for genetic diseases: inherited disorders affecting the lung and those mimicking sudden infant death syndrome.Human gene therapy · 2012Review
- Recombinant adeno-associated virus vectors in the treatment of rare diseases.Expert opinion on orphan drugsArticle
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 × 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of intramuscular lipids in treated animals. Correction was not observed in liver tissue extracts, but cardiac muscle extracts showed significant reduction of long-chain metabolites. Disease-specific phenotypes were characterized, including thermoregulation and maintenance of euglycemia after a fasting cold challenge. Internal body temperatures of untreated VLCAD(-/-) mice dropped below 20 °C and the mice became lethargic, requiring euthanasia. In contrast, all rAAV9-treated VLCAD(-/-) mice and the wild-type controls maintained body temperatures. rAAV9-treated VLCAD(-/-) mice maintained euglycemia, whereas untreated VLCAD(-/-) mice suffered hypoglycemia following a fasting cold challenge. These promising results suggest rAAV9 gene therapy as a potential treatment for VLCAD deficiency in humans.
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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.