ArticleProceedings of the National Academy of Sciences of the United States of America2016
Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
- Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1).Neurology · 2017Trial
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- Proof-of-principle of NF1 gene therapy in plexiform neurofibroma xenograft mouse models.Communications biology · 2026Article
- Pathologic and Therapeutic Schwann Cells.Cells · 2025Review
- A dose escalation and safety study of AAVrh10-mediated Schwann cell-targeted gene therapy for CMT1X.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Developing a gene therapy for Charcot-Marie-Tooth disease: progress and challenges.Regenerative medicine · 2025Review
- New perspectives for gene therapy of the X-linked form of Charcot-Marie-Tooth disease.Molecular therapy. Methods & clinical development · 2024Article
- AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Intravenous Administration of an AAV9 Vector Ubiquitously Expressing C1orf194 Gene Improved CMT-Like Neuropathy in C1orf194Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Gene replacement therapy in two Golgi-retained CMT1X mutants before and after the onset of demyelinating neuropathy.Molecular therapy. Methods & clinical development · 2023Article
- X-linked Charcot Marie Tooth mutations alter COFrontiers in cellular neuroscience · 2023Article
- Sensory Nerve Maintains Intervertebral Disc Extracellular Matrix Homeostasis Via CGRP/CHSY1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics.Biomedicines · 2022Review
- AAV1.NT-3 gene therapy for X-linked Charcot-Marie-Tooth neuropathy type 1.Gene therapy · 2022Article
- Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery.Scientific reports · 2021Article
- AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy.Gene therapy · 2021Article
- Challenges in Treating Charcot-Marie-Tooth Disease and Related Neuropathies: Current Management and Future Perspectives.Brain sciences · 2021Review
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies.
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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.