Document Type
Article
Publication Date
6-8-2023
Abstract
Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) enzyme, leading to the accumulation of glycosaminoglycans (GAG), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), mainly in cartilage and bone. This lysosomal storage disorder (LSD) is characterized by severe systemic skeletal dysplasia. To this date, none of the treatment options for the MPS IVA patients correct bone pathology. Enzyme replacement therapy with elosulfase alpha provides a limited impact on bone growth and skeletal lesions in MPS IVA patients. To improve bone pathology, we propose a novel gene therapy with a small peptide as a growth-promoting agent for MPS IVA. A small molecule in this peptide family has been found to exert biological actions over the cardiovascular system. This work shows that an AAV vector expressing a C-type natriuretic (CNP) peptide induces bone growth in the MPS IVA mouse model. Histopathological analysis showed the induction of chondrocyte proliferation. CNP peptide also changed the pattern of GAG levels in bone and liver. These results suggest the potential for CNP peptide to be used as a treatment in MPS IVA patients.
Recommended Citation
Rintz, Estera; Herreño-Pachón, Angélica María; Celik, Betul; Nidhi, Fnu; Khan, Shaukat; Benincore-Flórez, Eliana; and Tomatsu, Shunji, "Bone Growth Induction in Mucopolysaccharidosis IVA Mouse" (2023). Department of Pediatrics Faculty Papers. Paper 139.
https://jdc.jefferson.edu/pedsfp/139
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Supplementary Materials
Language
English
Comments
This article is the author's final published version in the International Journal of Molecular Sciences, Volume 24, Issue 12, 2023, Article number 9890.
The published version is available at https://doi.org/10.3390/ijms24129890. Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland.