Response to Comments on "Increasing Enzyme Mannose-6-Phosphate Levels but Not Miglustat Coadministration Enhances the Efficacy of Enzyme Replacement Therapy in Pompe Mice".
| Autor: | George K; Metabolic and Lysosomal Storage Disease Research, Rare and Neurologic Diseases Therapeutic Area, Sanofi, Cambridge, Massachusetts kelly.george@sanofi.com., Anding A; Metabolic and Lysosomal Storage Disease Research, Rare and Neurologic Diseases Therapeutic Area, Sanofi, Cambridge, Massachusetts. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2024 May 21; Vol. 389 (3), pp. 313-314. Date of Electronic Publication: 2024 May 21. |
| DOI: | 10.1124/jpet.123.002080 |
| Abstrakt: | We thank Dr. Weimer and her colleagues for their comments related to our recent work (Anding et al., 2023) and are grateful for the opportunity to further discuss the importance of efficient lysosomal targeting of enzyme-replacement therapies (ERT) for the treatment of Pompe disease. Patients with Pompe disease have mutations in the gene that encodes for acid α glucosidase (GAA), a lysosomal enzyme necessary for the breakdown of glycogen. The first-generation ERT, alglucosidase alfa, provides a lifesaving therapy for the severe form of the disease (infantile onset Pompe disease) and improves or stabilizes respiratory and motor function in patients with less severe disease (late onset Pompe disease). Despite these gains, significant unmet need remains, particularly in patients who display respiratory and motor decline following years of treatment. Poor tissue uptake and lysosomal targeting via inefficient binding of the cation-independent mannose-6-phosphate (M6P) receptor (CIMPR) in skeletal muscle contributed to this suboptimal treatment response, prompting the development of new ERTs with increased levels of M6P. (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.) |
| Databáze: | MEDLINE |
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