Innovative approach in Pompe disease therapy: Induction of immune tolerance by antigen-encapsulated red blood cells
| Autor: | Willy Berlier, Quitterie Barthe, Gaelle Campello, Yann Godfrin, Nathalie Guerin, Françoise Horand, Magali Cremel |
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| Rok vydání: | 2015 |
| Předmět: |
Erythrocytes
medicine.medical_treatment education Pharmaceutical Science Immune tolerance Mice Immune system Antigen Immune Tolerance medicine Animals Glycogen storage disease Antigens reproductive and urinary physiology biology Glycogen Storage Disease Type II business.industry alpha-Glucosidases Enzyme replacement therapy medicine.disease female genital diseases and pregnancy complications Immunity Humoral Mice Inbred C57BL body regions Tolerance induction Immunology biology.protein Antibody business Adjuvant |
| Zdroj: | International Journal of Pharmaceutics. 491:69-77 |
| ISSN: | 0378-5173 |
| Popis: | Pompe disease is a glycogen storage disease caused by acid α-glucosidase enzyme deficiency. Currently, the unique treatment is lifelong enzyme replacement therapy ERT with frequent intravenous administration of the recombinant analog alglucosidase-α (AGA), which ultimately generates a sustained humoral response resulting in treatment discontinuation. Our aim is to use the tolerogenic properties of antigen-encapsulated red blood cells (RBCs) to abolish the humoral response against AGA and to restore tolerance to replacement therapy. To demonstrate that our approach could prevent the AGA-induced immune response, mice were intravenously injected three times with AGA encapsulated into RBCs before being sensitized to AGA with several adjuvant molecules. Control animals received injections of free AGA instead of the encapsulated molecule. One-week after treatment with AGA-loaded RBCs, a strong decrease in specific humoral response was observed despite three stimulations with AGA and adjuvant molecules. Furthermore, this specific immunomodulation was maintained for at least two months without affecting the overall immune response. AGA-loaded RBCs represent a promising strategy to induce or restore tolerance in Pompe disease patients who develop hypersensitivity reactions following repeated AGA administrations. |
| Databáze: | OpenAIRE |
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