ArticleThe Journal of clinical investigation2016
PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 102 citations in OpenAlex.
- Trial
- X-linked myotubular myopathy, liver disease, and gene therapy.Journal of neuromuscular diseases · 2026Review
- Pharmacological PIK3C2B inhibition rescues XLMTM phenotype in mouse models and identifies molecular markers of disease.JCI insight · 2026Article
- Beyond Membrane Remodeling: Organelle Crosstalk and Convergent Pathology in Centronuclear Myopathy.Muscles (Basel, Switzerland) · 2026Review
- Caloric restriction reprograms skeletal muscle molecular pathways in non-human primates: potential relevance to human aging biology.Skeletal muscle · 2026Article
- Lysosomal phosphoinositide turnover acts upstream of RagGTPase-mTORC1 and controls muscle growth.Nature metabolism · 2026Article
- Lack of myotubularin phosphatase activity is the main cause of X-linked myotubular myopathy.JCI insight · 2025Article
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 2025Review
- microRNA-133a as an indicator of disease progression and treatment response in X-linked myotubular myopathy.Molecular therapy. Nucleic acids · 2025Article
- Characterization of a novel zebrafish model ofBrain communications · 2025Article
- Potential compensatory mechanisms preserving cardiac function in myotubular myopathy.Cellular and molecular life sciences : CMLS · 2024Article
- Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.Science (New York, N.Y.) · 2024Article
- Aligning with the 3Rs: alternative models for research into muscle development and inherited myopathies.BMC veterinary research · 2024Review
- 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
- Phosphoinositide switches in cell physiology - From molecular mechanisms to disease.The Journal of biological chemistry · 2024Review
- Standardization of zebrafish drug testing parameters for muscle diseases.Disease models & mechanisms · 2024Article
- Loss of Mtm1 causes cholestatic liver disease in a model of X-linked myotubular myopathy.The Journal of clinical investigation · 2023Article
- 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
- Inactivating the lipid kinase activity of PI3KC2β is sufficient to rescue myotubular myopathy in mice.JCI insight · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
5 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
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myotubular myopathy (MTM) is a devastating pediatric neuromuscular disorder of phosphoinositide (PIP) metabolism resulting from mutations of the PIP phosphatase MTM1 for which there are no treatments. We have previously shown phosphatidylinositol-3-phosphate (PI3P) accumulation in animal models of MTM. Here, we tested the hypothesis that lowering PI3P levels may prevent or reverse the MTM disease process. To test this, we targeted class II and III PI3 kinases (PI3Ks) in an MTM1-deficient mouse model. Muscle-specific ablation of Pik3c2b, but not Pik3c3, resulted in complete prevention of the MTM phenotype, and postsymptomatic targeting promoted a striking rescue of disease. We confirmed this genetic interaction in zebrafish, and additionally showed that certain PI3K inhibitors prevented development of the zebrafish mtm phenotype. Finally, the PI3K inhibitor wortmannin improved motor function and prolonged lifespan of the Mtm1-deficient mice. In all, we have identified Pik3c2b as a genetic modifier of Mtm1 mutation and demonstrated that PIK3C2B inhibition is a potential treatment strategy for MTM. In addition, we set the groundwork for similar reciprocal inhibition approaches for treating other PIP metabolic disorders and highlight the importance of modifier gene pathways as therapeutic targets.
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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.