title: BAFF blockade prevents anti-drug antibody formation in a mouse model of Pompe disease.
abstract: Antibodies formed against the therapeutic protein are a life-threatening complication that arises during enzyme replacement therapy for Pompe disease (acid α-glucosidase deficiency; GAA). To provide an effective alternative to current practices, we investigated the capacity of anti-B-cell activating factor (BAFF) as a novel drug candidate to prevent antibody formation in a Pompe disease mouse model. A BAFF-neutralizing antibody was administered prophylactically and with maintenance doses in association with enzyme replacement therapy using recombinant human GAA in Gaa(-/-) mice. BAFF blockade delayed antibody production and increased GAA activity within tissues with protection from anaphylaxis. Anti-BAFF also resolved antibody formation during an immune response and precluded the maturation of antibody secreting cells from entering the bone marrow compartment. This treatment modality may therefore be a viable alternative for the clinical management of antibody formation for Pompe disease and has potential use against antibody formation in other protein replacement therapies.
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL, USA. Electronic address: pdoerfler@ufl.edu.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Doerfler
authors.affiliation: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Sushrusha
authors.initials: S
authors.lastname: Nayak
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL, USA.
authors.forename: Roland W
authors.initials: RW
authors.lastname: Herzog
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL, USA. Electronic address: bbyrne@ufl.edu.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Byrne
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D056947:Enzyme Replacement Therapy; D005260:Female; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D015316:Genetic Therapy / Q000379:methods; D005087:Glucan 1,4-alpha-Glucosidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; D053264:B-Cell Activating Factor; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D005087:Glucan 1,4-alpha-Glucosidase
keywords: Acid alpha-glucosidase; BAFF; BLyS; Enzyme replacement therapy; Pompe disease
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