Correction of oxidative stress enhances enzyme replacement therapy in Pompe disease
| Autor: | Marcella Coletta, Daria Maria Monti, Carla Damiano, Sandra Strollo, Roman S. Polishchuk, Alessia Indrieri, Roberta Iacono, Francesca Zappa, Maria Antonietta De Matteis, Elena Polishchuk, Giancarlo Parenti, Edoardo Nusco, Simona Fecarotta, Nadia Minopoli, Diego L. Medina, Caterina Porto, Antonietta Tarallo, Marco Moracci, Paola Imbimbo |
|---|---|
| Přispěvatelé: | Tarallo, A., Damiano, C., Strollo, S., Minopoli, N., Indrieri, A., Polishchuk, E., Zappa, F., Nusco, E., Fecarotta, S., Porto, C., Coletta, M., Iacono, R., Moracci, M., Polishchuk, R., Medina, D. L., Imbimbo, P., Monti, D. M., De Matteis, M. A., Parenti, G. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Medicine (General)
Metabolic myopathy QH426-470 Pharmacology Resveratrol medicine.disease_cause Article chemistry.chemical_compound Mice R5-920 Genetics Edaravone medicine Idebenone Animals Humans alpha-glucosidase alpha‐glucosidase N‐acetylcysteine Musculoskeletal System oxidative stre Glycogen business.industry Glycogen Storage Disease Type II Autophagy Pompe disease alpha-Glucosidases Enzyme replacement therapy Articles medicine.disease N-acetylcysteine Oxidative Stress Metabolism chemistry Molecular Medicine Genetics Gene Therapy & Genetic Disease business Oxidative stress medicine.drug enzyme replacement therapy |
| Zdroj: | EMBO Molecular Medicine EMBO Molecular Medicine, Vol 13, Iss 11, Pp n/a-n/a (2021) |
| Popis: | Pompe disease is a metabolic myopathy due to acid alpha‐glucosidase deficiency. In addition to glycogen storage, secondary dysregulation of cellular functions, such as autophagy and oxidative stress, contributes to the disease pathophysiology. We have tested whether oxidative stress impacts on enzyme replacement therapy with recombinant human alpha‐glucosidase (rhGAA), currently the standard of care for Pompe disease patients, and whether correction of oxidative stress may be beneficial for rhGAA therapy. We found elevated oxidative stress levels in tissues from the Pompe disease murine model and in patients’ cells. In cells, stress levels inversely correlated with the ability of rhGAA to correct the enzymatic deficiency. Antioxidants (N‐acetylcysteine, idebenone, resveratrol, edaravone) improved alpha‐glucosidase activity in rhGAA‐treated cells, enhanced enzyme processing, and improved mannose‐6‐phosphate receptor localization. When co‐administered with rhGAA, antioxidants improved alpha‐glucosidase activity in tissues from the Pompe disease mouse model. These results indicate that oxidative stress impacts on the efficacy of enzyme replacement therapy in Pompe disease and that manipulation of secondary abnormalities may represent a strategy to improve the efficacy of therapies for this disorder. Enzyme replacement therapy (ERT) with recombinant human alpha‐glucosidase (rhGAA) is currently the standard of care for the treatment of Pompe disease. However, this approach shows important limitations. We have tested whether modulation of oxidative stress may improve the efficacy of ERT. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|