ArticleBrain : a journal of neurology2023
Downregulation of PMP22 ameliorates myelin defects in iPSC-derived human organoid cultures of CMT1A.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.Nature reviews. Neuroscience · 2026Review
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- The Charcot-Marie-Tooth Neuropathy (CMTX3) Complex Structural Variation Causes Differential SOX3 Spatiotemporal Expression.Human mutation · 2026Article
- [Generation of induced pluripotent stem cells from peripheral blood mononuclear cells of a patient with autosomal recessive CharcotZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Advances and challenges in modeling Charcot-Marie-Tooth type 2A using iPSC-derived models.Stem cell reports · 2025Review
- The current status of Charcot-Marie-Tooth disease type 1 A treatment.Acta neurologica Belgica · 2025Review
- Characterising PMP22-Proximal Partners in a Schwann Cell Model of Charcot-Marie-Tooth Disease Type1A.Biology · 2025Article
- Organoids in Genetic Disorders: from Disease Modeling to Translational Applications.Stem cell reviews and reports · 2025Review
- Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy.Annals of clinical and translational neurology · 2025Review
- Biomedical applications of organoids in genetic diseases.Medical review (2021) · 2025Review
- Modeling of Charcot-Marie-Tooth disease in zebrafish.Frontiers in molecular neuroscience · 2025Review
- Role of glial cells in motor neuron degeneration in hereditary spastic paraplegias.Frontiers in cellular neuroscience · 2025Review
- An Overview of Oligodendrocyte Metabolism.Advances in neurobiology · 2025Review
- Advances in mesenchymal stem cells and their derivatives for promoting peripheral nerve regeneration.Burns & trauma · 2025Review
- Current Treatment Methods for Charcot-Marie-Tooth Diseases.Biomolecules · 2024Review
- PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells.Brain : a journal of neurology · 2024Article
- Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches.International journal of molecular sciences · 2024Review
- hESC- and hiPSC-derived Schwann cells are molecularly comparable and functionally equivalent.iScience · 2024Article
- Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.Experimental & molecular medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Charcot-Marie-Tooth disease is the most common inherited disorder of the PNS. CMT1A accounts for 40-50% of all cases and is caused by a duplication of the PMP22 gene on chromosome 17, leading to dysmyelination in the PNS. Patient-derived models to study such myelination defects are lacking as the in vitro generation of human myelinating Schwann cells has proved to be particularly challenging. Here, we present an induced pluripotent stem cell-derived organoid culture, containing various cell types of the PNS, including myelinating human Schwann cells, which mimics the human PNS. Single-cell analysis confirmed the PNS-like cellular composition and provides insight into the developmental trajectory. We used this organoid model to study disease signatures of CMT1A, revealing early ultrastructural myelin alterations, including increased myelin periodic line distance and hypermyelination of small axons. Furthermore, we observed the presence of onion-bulb-like formations in a later developmental stage. These hallmarks were not present in the CMT1A-corrected isogenic line or in a CMT2A iPSC line, supporting the notion that these alterations are specific to CMT1A. Downregulation of PMP22 expression using short-hairpin RNAs or a combinatorial drug consisting of baclofen, naltrexone hydrochloride and D-sorbitol was able to ameliorate the myelin defects in CMT1A-organoids. In summary, this self-organizing organoid model can capture biologically meaningful features of the disease and capture the physiological complexity, forms an excellent model for studying demyelinating diseases and supports the therapeutic approach of reducing PMP22 expression.
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.