ArticlePathoGenetics2008
Abnormal mannose-6-phosphate receptor trafficking impairs recombinant alpha-glucosidase uptake in Pompe disease fibroblasts.
Article in PathoGenetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease.Nature communications · 2024Trial
- Duvoglustat HCl Increases Systemic and Tissue Exposure of Active Acid α-Glucosidase in Pompe Patients Co-administered with Alglucosidase α.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Trial
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- TRPML1 agonists synergize with enzyme replacement therapy in fibroblasts from Pompe disease patients.Journal of translational medicine · 2026Article
- Investigation into the Anti-hyperglycemic Traits and Bioactive Constituents of Postbiotics Derived from Lacticaseibacillus paracasei NCUH012072.Probiotics and antimicrobial proteins · 2026Article
- Cipaglucosidase alfa plus miglustat: linking mechanism of action to clinical outcomes in late-onset Pompe disease.Frontiers in neurology · 2024Article
- Population pharmacokinetic modeling and dosing simulation of avalglucosidase alfa for selecting alternative dosing regimen in pediatric patients with late-onset pompe disease.Journal of pharmacokinetics and pharmacodynamics · 2023Article
- Polymer-based drug delivery systems under investigation for enzyme replacement and other therapies of lysosomal storage disorders.Advanced drug delivery reviews · 2023Review
- Isogenic GAA-KO Murine Muscle Cell Lines Mimicking Severe Pompe Mutations as Preclinical Models for the Screening of Potential Gene Therapy Strategies.International journal of molecular sciences · 2022Article
- Gene Therapy Developments for Pompe Disease.Biomedicines · 2022Review
- Correction of oxidative stress enhances enzyme replacement therapy in Pompe disease.EMBO molecular medicine · 2021Article
- Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates.Nature communications · 2021Article
- New Insights into Gastrointestinal Involvement in Late-Onset Pompe Disease: Lessons Learned from Bench and Bedside.Journal of clinical medicine · 2021Article
- Three-dimensional tissue-engineered human skeletal muscle model of Pompe disease.Communications biology · 2021Article
- Intermittent enzyme replacement therapy with recombinant human β-galactosidase prevents neuraminidase 1 deficiencyThe Journal of biological chemistry · 2020Article
- Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment.Journal of virology · 2020Article
- Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences.Molecular genetics and metabolism reports · 2020Article
- Rapid Clathrin-Mediated Uptake of Recombinant α-Gal-A to Lysosome Activates Autophagy.Biomolecules · 2020Article
- Article
- Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery.Biomimetics (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPompe disease (PD) is a metabolic myopathy caused by alpha-glucosidase (GAA) deficiency and characterized by generalized glycogen storage. Heterogeneous GAA gene mutations result in wide phenotypic variability, ranging from the severe classic infantile presentation to the milder intermediate and late-onset forms. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA), the only treatment available for PD, intriguingly shows variable efficacy in different PD patients. To investigate the mechanisms underlying the variable response to ERT, we studied cell morphology of PD fibroblasts, the distribution and trafficking of the cation-independent mannose-6-phosphate receptor (CI-MPR) that mediates rhGAA uptake, and rhGAA uptake itself.
resultsWe observed abnormalities of cell morphology in PD cells. Electron microscopy analysis showed accumulation of multivesicular bodies and expansion of the Golgi apparatus, and immunolocalization and western blot analysis of LC3 showed activation of autophagy. Immunofluorescence analysis showed abnormal intracellular distribution of CI-MPR in PD fibroblasts, increased co-localization with LC3 and reduced availability of the receptor at the plasma membrane. The recycling of CI-MPR from the plasma membrane to the trans-Golgi network was also impaired. All these abnormalities were more prominent in severe and intermediate PD fibroblasts, correlating with disease severity. In severe and intermediate PD cells rhGAA uptake and processing were less efficient and correction of GAA activity was reduced.
conclusionThese results indicate a role for disrupted CI-MPR trafficking in the variable response to ERT in PD and have implications for ERT efficacy and optimization of treatment protocols.
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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.