title: Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder.
abstract: Temporary interruption of enzyme replacement therapy (ERT) in patients with different lysosomal storage disorders may happen for different reasons (adverse reactions, issues with reimbursement, logistic difficulties, and so forth), and the impact of the interruption is still uncertain. In the present work, we studied the effects of the interruption of intravenous ERT (Laronidase, Genzyme) followed by its reintroduction in mice with the prototypical lysosomal storage disorder mucopolysaccharidosis type I, comparing to mice receiving continuous treatment, untreated mucopolysaccharidosis type I mice, and normal mice. In the animals which treatment was temporarily interrupted, we observed clear benefits of treatment in several organs (liver, lung, heart, kidney, and testis) after reintroduction, but a worsening in the thickness of the aortic wall was detected. Furthermore, these mice had just partial improvements in behavioral tests, suggesting some deterioration in the brain function. Despite worsening is some disease aspects, urinary glycosaminoglycans levels did not increase during interruption, which indicates that this biomarker commonly used to monitor treatment in patients should not be used alone to assess treatment efficacy. The deterioration observed was not caused by the development of serum antienzyme antibodies. All together our results suggest that temporary ERT interruption leads to deterioration of function in some organs and should be avoided whenever possible.
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Schneider
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, UFRGS, Porto Alegre, Brazil. Electronic address: umatte@hcpa.edu.br.
authors.forename: Ursula
authors.initials: U
authors.lastname: Matte
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, UFRGS, Porto Alegre, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pasqualim
authors.affiliation: Programa de Pós-Graduação em Ciência Biológicas: Fisiologia, UFRGS, Porto Alegre, Brazil.
authors.forename: Angela Maria Vicente
authors.initials: AM
authors.lastname: Tavares
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil.
authors.forename: Fabiana Quoos
authors.initials: FQ
authors.lastname: Mayer
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil.
authors.forename: Barbara
authors.initials: B
authors.lastname: Martinelli
authors.affiliation: Serviço de Genética Médica-HCPA, Porto Alegre, Brazil.
authors.forename: Graziela
authors.initials: G
authors.lastname: Ribas
authors.affiliation: Serviço de Genética Médica-HCPA, Porto Alegre, Brazil.
authors.forename: Carmen Regla
authors.initials: CR
authors.lastname: Vargas
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, UFRGS, Porto Alegre, Brazil; Serviço de Genética Médica-HCPA, Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Centro de Terapia Gênica- HCPA, Porto Alegre, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, UFRGS, Porto Alegre, Brazil; Programa de Pós-Graduação em Ciência Biológicas: Fisiologia, UFRGS, Porto Alegre, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Baldo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001011:Aorta / Q000473:pathology; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D004562:Electrocardiography; D056947:Enzyme Replacement Therapy; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006025:Glycosaminoglycans / Q000652:urine; D006334:Heart Function Tests; D051379:Mice; D008059:Mucopolysaccharidosis I / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy* / Q000652:urine
chemical_list: D000906:Antibodies; D005904:Glial Fibrillary Acidic Protein; D006025:Glycosaminoglycans