Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder
| Autor: | Gabriela Pasqualim, Angela Maria Vicente Tavares, Ana Paula Krauthein Schneider, Bárbara Zambiasi Martinelli, Fabiana Quoos Mayer, Roberto Giugliani, Ursula da Silveira Matte, Guilherme Baldo, Graziela S. Ribas, Carmen Regla Vargas |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Mucopolysaccharidosis Urinary system Mucopolysaccharidosis I Physiology Antibodies 03 medical and health sciences Mucopolysaccharidosis type I Electrocardiography Mice Physiology (medical) Internal medicine Glial Fibrillary Acidic Protein medicine Animals Enzyme Replacement Therapy Aorta Glycosaminoglycans Kidney Lung Behavior Animal business.industry Biochemistry (medical) Public Health Environmental and Occupational Health Brain General Medicine Enzyme replacement therapy medicine.disease 030104 developmental biology Endocrinology medicine.anatomical_structure Heart Function Tests Biomarker (medicine) business |
| Zdroj: | Translational research : the journal of laboratory and clinical medicine. 176 |
| ISSN: | 1878-1810 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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