ArticleJCI insight2019
Gene suppressing therapy for Pelizaeus-Merzbacher disease using artificial microRNA.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Comparative analysis of cell-specific promoters in AAV9-mediated gene therapy targeting the central nervous system.Molecular therapy. Methods & clinical development · 2025Article
- A lipid nanoparticle-based oligodendrocyte-specific mRNA therapy.Molecular therapy. Nucleic acids · 2024Article
- Focused Ultrasounds as an Adeno-Associated Virus Gene Therapy-Empowering Tool in Juvenile Mice via Intracerebroventricular Administration.Human gene therapy · 2024Article
- Pelizaeus-Merzbacher disease: on the cusp of myelin medicine.Trends in molecular medicine · 2024Review
- Molecular Pathogenic Mechanisms of Hypomyelinating Leukodystrophies (HLDs).Neurology international · 2023Review
- Effects of early maternal separation on the expression levels of hippocampal and prefrontal cortex genes and pathways in lactating piglets.Frontiers in molecular neuroscience · 2023Article
- miR-124 regulates early isolation-induced social abnormalities via inhibiting myelinogenesis in the medial prefrontal cortex.Cellular and molecular life sciences : CMLS · 2022Article
- Mutation of Proteolipid Protein 1 Gene: From Severe Hypomyelinating Leukodystrophy to Inherited Spastic Paraplegia.Biomedicines · 2022Review
- Identifying oligodendrocyte enhancers governing Plp1 expression.Human molecular genetics · 2021Article
- Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression.EMBO molecular medicine · 2021Article
- Hypomyelinating leukodystrophies - unravelling myelin biology.Nature reviews. Neurology · 2021Review
- Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.Frontiers in cellular neuroscience · 2021Review
- Article
- Neural stem cells restore myelin in a demyelinating model of Pelizaeus-Merzbacher disease.Brain : a journal of neurology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Copy number increase or decrease of certain dosage-sensitive genes may cause genetic diseases with distinct phenotypes, conceptually termed genomic disorders. The most common cause of Pelizaeus-Merzbacher disease (PMD), an X-linked hypomyelinating leukodystrophy, is genomic duplication encompassing the entire proteolipid protein 1 (PLP1) gene. Although the exact molecular and cellular mechanisms underlying PLP1 duplication, which causes severe hypomyelination in the central nervous system, remain largely elusive, PLP1 overexpression is likely the fundamental cause of this devastating disease. Here, we investigated if adeno-associated virus-mediated (AAV-mediated) gene-specific suppression may serve as a potential cure for PMD by correcting quantitative aberrations in gene products. We developed an oligodendrocyte-specific Plp1 gene suppression therapy using artificial microRNA under the control of human CNP promoter in a self-complementary AAV (scAAV) platform. A single direct brain injection achieved widespread oligodendrocyte-specific Plp1 suppression in the white matter of WT mice. AAV treatment in Plp1-transgenic mice, a PLP1 duplication model, ameliorated cytoplasmic accumulation of Plp1, preserved mature oligodendrocytes from degradation, restored myelin structure and gene expression, and improved survival and neurological phenotypes. Together, our results provide evidence that AAV-mediated gene suppression therapy can serve as a potential cure for PMD resulting from PLP1 duplication and possibly for other genomic disorders.
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