ArticleThe Journal of clinical investigation2022
A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 46 citations in OpenAlex.
- PXT3003: Lessons for therapeutic development in Charcot-Marie-Tooth disease type 1A and related neuropathies.iScience · 2026Review
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Safety, efficacy, and distal nerve Schwann cell biodistribution in mice and NHPs to support translation of AAV9 RNAi therapy for CMT1A.Molecular therapy. Nucleic acids · 2026Article
- Development ofMolecular therapy. Advances · 2026Article
- Review
- Identification and Targeted Correction of a PathogenicInternational journal of molecular sciences · 2026Article
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 2026Review
- Hereditary Polyneuropathies in the Era of Precision Medicine: Genetic Complexity and Emerging Strategies.Genes · 2026Review
- Bridging science and hope: the evolving story of gene therapy for neuromuscular diseases.Frontiers in cell and developmental biology · 2026Review
- The current status of Charcot-Marie-Tooth disease type 1 A treatment.Acta neurologica Belgica · 2025Review
- Perineural delivery of AAV2/9 in non-human primates is a safe and efficient route for gene therapy in Charcot-Marie-Tooth diseases.Molecular therapy. Methods & clinical development · 2025Article
- Pathologic and Therapeutic Schwann Cells.Cells · 2025Review
- Nerve Diameter and DTI Parameters Maybe Potential Markers for Clinical Trial in Patients With Charcot-Marie-Tooth Disease Type 1A.European journal of neurology · 2025Article
- Developing a gene therapy for Charcot-Marie-Tooth disease: progress and challenges.Regenerative medicine · 2025Review
- Selective RNAi silencing of Schwann cell Piezo1 alleviates mechanical hypersensitization following peripheral nerve injury.Molecular therapy. Methods & clinical development · 2025Article
- The neurological damage caused by enterovirus 71 infection is associated with hsa_circ_0069335/miR-29b/PMP22 pathway.Journal of virology · 2025Article
- Characterization of a humanized mouse model of Charcot-Marie-Tooth type 1A for the discovery of humanFrontiers in neurology · 2025Article
- Identification of common diagnostic genes and molecular pathways in endometriosis and systemic lupus erythematosus by machine learning approach and in vitro experiment.International journal of medical sciences · 2025Article
- A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?International journal of molecular sciences · 2024Review
- Review
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited demyelinating peripheral neuropathy, is caused by PMP22 gene duplication. Overexpression of WT PMP22 in Schwann cells destabilizes the myelin sheath, leading to demyelination and ultimately to secondary axonal loss and disability. No treatments currently exist that modify the disease course. The most direct route to CMT1A therapy will involve reducing PMP22 to normal levels. To accomplish this, we developed a gene therapy strategy to reduce PMP22 using artificial miRNAs targeting human PMP22 and mouse Pmp22 mRNAs. Our lead therapeutic miRNA, miR871, was packaged into an adeno-associated virus 9 (AAV9) vector and delivered by lumbar intrathecal injection into C61-het mice, a model of CMT1A. AAV9-miR871 efficiently transduced Schwann cells in C61-het peripheral nerves and reduced human and mouse PMP22 mRNA and protein levels. Treatment at early and late stages of the disease significantly improved multiple functional outcome measures and nerve conduction velocities. Furthermore, myelin pathology in lumbar roots and femoral motor nerves was ameliorated. The treated mice also showed reductions in circulating biomarkers of CMT1A. Taken together, our data demonstrate that AAV9-miR871-driven silencing of PMP22 rescues a CMT1A model and provides proof of principle for treating CMT1A using a translatable gene therapy approach.
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