ArticleHuman molecular genetics2008
AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01840657 (Prospective Study of Adverse Event Rates in Males With X-Linked Myotubular Myopathy), which is not on this map. Cited by 71 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.
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.
Prospective Study of Adverse Event Rates in Males With X-Linked Myotubular Myopathy
Who cites it
71 citing papers in PubMed, 126 citations in OpenAlex.
- High-throughput transcriptome analyses from ASPIRO, a phase 1/2/3 study of gene replacement therapy for X-linked myotubular myopathy.American journal of human genetics · 2023Trial
- Trial
- X-linked myotubular myopathy, liver disease, and gene therapy.Journal of neuromuscular diseases · 2026Review
- Tamoxifen treatment fails to improve muscle dysfunction in a model of recessive RYR1-linked centronuclear myopathy.Disease models & mechanisms · 2025Article
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Architecture and molecular machinery of skeletal myofibers: a systematic review of the structure-function relationships.Frontiers in cell and developmental biology · 2025Review
- A healthcare claims analysis to identify and characterize patients with suspected X-Linked Myotubular Myopathy (XLMTM) in the Brazilian Healthcare System.Orphanet journal of rare diseases · 2024Article
- Real-world analysis of healthcare resource utilization by patients with X-linked myotubular myopathy (XLMTM) in the United States.Orphanet journal of rare diseases · 2023Article
- Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders.Science advances · 2022Article
- Natural history study and statistical modeling of disease progression in a preclinical model of myotubular myopathy.Disease models & mechanisms · 2022Article
- A dog model for centronuclear myopathy carrying the most common DNM2 mutation.Disease models & mechanisms · 2022Article
- The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites.Biomolecules · 2022Review
- Mature Myotubes Generated From Human-Induced Pluripotent Stem Cells Without Forced Gene Expression.Frontiers in cell and developmental biology · 2022Article
- INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy.Journal of neuromuscular diseases · 2022Article
- Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.International journal of molecular sciences · 2021Review
- Hepatobiliary disease in XLMTM: a common comorbidity with potential impact on treatment strategies.Orphanet journal of rare diseases · 2021Article
- Multi-omics comparisons of different forms of centronuclear myopathies and the effects of several therapeutic strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- T-tubule remodeling in human hypertrophic cardiomyopathy.Journal of muscle research and cell motility · 2021Review
- Current Clinical Applications of In Vivo Gene Therapy with AAVs.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases.International journal of molecular sciences · 2020Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Myotubular myopathy (XLMTM, OMIM 310400) is a severe congenital muscular disease due to mutations in the myotubularin gene (MTM1) and characterized by the presence of small myofibers with frequent occurrence of central nuclei. Myotubularin is a ubiquitously expressed phosphoinositide phosphatase with a muscle-specific role in man and mouse that is poorly understood. No specific treatment exists to date for patients with myotubular myopathy. We have constructed an adeno-associated virus (AAV) vector expressing myotubularin in order to test its therapeutic potential in a XLMTM mouse model. We show that a single intramuscular injection of this vector in symptomatic Mtm1-deficient mice ameliorates the pathological phenotype in the targeted muscle. Myotubularin replacement in mice largely corrects nuclei and mitochondria positioning in myofibers and leads to a strong increase in muscle volume and recovery of the contractile force. In addition, we used this AAV vector to overexpress myotubularin in wild-type skeletal muscle and get insight into its localization and function. We show that a substantial proportion of myotubularin associates with the sarcolemma and I band, including triads. Myotubularin overexpression in muscle induces the accumulation of packed membrane saccules and presence of vacuoles that contain markers of sarcolemma and T-tubules, suggesting that myotubularin is involved in plasma membrane homeostasis of myofibers. This study provides a proof-of-principle that local delivery of an AAV vector expressing myotubularin can improve the motor capacities of XLMTM muscle and represents a novel approach to study myotubularin function in skeletal muscle.
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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.