How Pompe Disease Affects Enzyme Uptake in Cells
Author Information
Author(s): Monica Cardone, Caterina Porto, Antonietta Tarallo, Mariela Vicinanza, Barbara Rossi, Elena Polishchuk, Francesca Donaudy, Generoso Andria, Maria Antonietta De Matteis, Giancarlo Parenti
Primary Institution: Telethon Institute of Genetics and Medicine
Hypothesis
An impairment of housekeeping cellular functions and membrane trafficking resulting from abnormal substrate storage influences the efficacy of enzyme replacement therapy in Pompe disease.
Conclusion
Disrupted trafficking of the mannose-6-phosphate receptor impairs the uptake of the enzyme used in treatment, affecting the efficacy of enzyme replacement therapy in Pompe disease.
Supporting Evidence
- Fibroblasts from severe and intermediate Pompe disease patients showed reduced CI-MPR availability at the plasma membrane.
- Uptake of rhGAA was less efficient in fibroblasts from patients with severe phenotypes.
- CI-MPR trafficking was impaired in Pompe disease fibroblasts, correlating with disease severity.
- Longer incubation with rhGAA improved enzyme activity in severe Pompe disease fibroblasts.
Takeaway
Pompe disease makes it hard for cells to take in a special enzyme they need, which can make treatment less effective.
Methodology
The study involved analyzing fibroblasts from Pompe disease patients to assess cell morphology, CI-MPR distribution, and rhGAA uptake using electron microscopy, immunofluorescence, and western blot analysis.
Potential Biases
Potential bias in the selection of patient samples and the interpretation of results based on the severity of the disease.
Limitations
The study was limited to fibroblast cell lines and may not fully represent the in vivo situation in patients.
Participant Demographics
Fibroblast cell lines from five patients with varying phenotypes of Pompe disease.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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