Document Type

Article

Publication Date

10-29-2025

Comments

This article is the author’s final published version in Current Issues in Molecular Biology, Volume 47, Issue 11, 2025, Article number 900.

The published version is available at https://doi.org/10.3390/cimb47110900. Copyright © 2025 by the authors.

Abstract

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, which leads to the accumulation of chondroitin-6-sulfate and keratan sulfate, primarily in cartilage and its extracellular matrix, resulting in a direct impact on cartilage and bone development, as well as subsequent systemic skeletal dysplasia. ERT and HSCT are current treatment options, but they have a limited effect on bone lesions. In this article, we investigated liver-specific AAV8 vectors with a thyroxine-binding globulin promoter in the MPS IVA murine model to evaluate the long-term (24 weeks in males and 48 weeks in females) effects of gene therapy on biochemical markers and bone pathology. Both treated groups showed GALNS enzyme activity at supraphysiological levels in plasma and in various tissues, including the liver, heart, spleen, and bone. Keratan sulfate in both groups was normalized in plasma, liver, and bone (male mice). Pathological analyses revealed a decrease in vacuolated cells in the heart muscle and valves and improvement in bone pathology in treated male mice. However, the therapeutic impact was less pronounced in treated female mice. Overall, male mice indicated a substantial improvement in biochemical parameters and pathology compared to female mice.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Supplementary Materials.zip (572 kB)

PubMed ID

41296404

Language

English

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