ArticlePloS one2014
Immune responses and hypercoagulation in ERT for Pompe disease are mutation and rhGAA dose dependent.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Are Anti-rhGAA Antibodies a Determinant of Treatment Outcome in Adults with Late-Onset Pompe Disease? A Systematic Review.Biomolecules · 2023Pooled it
- What's new and what's next for gene therapy in Pompe disease?Expert opinion on biological therapy · 2022Pooled it
- Analyzing immune cell infiltrates in skeletal muscle of infantile-onset Pompe disease using bioinformatics and machine learning.Scientific reports · 2024Article
- Antibodies against recombinant human alpha-glucosidase do not seem to affect clinical outcome in childhood onset Pompe disease.Orphanet journal of rare diseases · 2022Article
- Uptake of moss-derived human recombinant GAA inJIMD reports · 2021Article
- Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families.International journal of molecular sciences · 2021Article
- Targeting Macromolecules to CNS and Other Hard-to-Treat Organs Using Lectin-Mediated Delivery.International journal of molecular sciences · 2020Review
- TLR9 signaling mediates adaptive immunity following systemic AAV gene therapy.Cellular immunology · 2019Article
- Pompe disease gene therapy: neural manifestations require consideration of CNS directed therapy.Annals of translational medicine · 2019Review
- Alternative Start Sites Downstream of Non-Sense Mutations Drive Antigen Presentation and Tolerance Induction to C-Terminal Epitopes.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy.Genetics in medicine : official journal of the American College of Medical Genetics · 2017Article
- Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients.Scientific reports · 2016Article
- Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State.Antimicrobial agents and chemotherapy · 2016Article
- Targeted approaches to induce immune tolerance for Pompe disease therapy.Molecular therapy. Methods & clinical development · 2016Review
- Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease.Human gene therapy · 2016Article
- Oral delivery of Acid Alpha Glucosidase epitopes expressed in plant chloroplasts suppresses antibody formation in treatment of Pompe mice.Plant biotechnology journal · 2015Article
- BAFF blockade prevents anti-drug antibody formation in a mouse model of Pompe disease.Clinical immunology (Orlando, Fla.) · 2015Article
- Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice.Molecular therapy. Methods & clinical development · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Enzyme replacement therapy (ERT) with recombinant human acid-α-glucosidase (rhGAA) is the only FDA approved therapy for Pompe disease. Without ERT, severely affected individuals (early onset) succumb to the disease within 2 years of life. A spectrum of disease severity and progression exists depending upon the type of mutation in the GAA gene (GAA), which in turn determines the amount of defective protein produced and its enzymatic activity. A large percent of the early onset patients are also cross reactive immunological material negative (CRIM-) and develop high titer immune responses to ERT with rhGAA. New insights from our studies in pre-clinical murine models reveal that the type of Gaa mutation has a profound effect on the immune responses mounted against ERT and the associated toxicities, including activation of clotting factors and disseminated intravascular coagulation (DIC). Additionally, the mouse strain affects outcomes, suggesting the influence of additional genetic components or modifiers. High doses of rhGAA (20 mg/kg) are currently required to achieve therapeutic benefit. Our studies indicate that lower enzyme doses reduce the antibody responses to rhGAA, reduce the incidence of immune toxicity and avoid ERT-associated anaphylaxis. Therefore, development of rhGAA with increased efficacy is warranted to limit immunotoxicities.
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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.