title: Innovative approach in Pompe disease therapy: Induction of immune tolerance by antigen-encapsulated red blood cells.
abstract: 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.
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Cremel
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guerin
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Campello
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Quitterie
authors.initials: Q
authors.lastname: Barthe
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Willy
authors.initials: W
authors.lastname: Berlier
authors.affiliation: ERYTECH Pharma, Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Horand
authors.affiliation: ERYTECH Pharma, Lyon, France. Electronic address: ygodfrin@erytech.com.
authors.forename: Yann
authors.initials: Y
authors.lastname: Godfrin
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology*; D006009:Glycogen Storage Disease Type II / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000520:alpha-Glucosidases / Q000276:immunology
chemical_list: D000941:Antigens; C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: Alglucosidase-α; Antibodies; Pompe disease; RBCs; Tolerance induction