Therapies of mucopolysaccharidosis IVA (Morquio A syndrome)

Abstract

Introduction: Morquio A syndrome (mucopolysaccharidosis type IVA, MPS IVA) is one of the lysosomal storage diseases and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme leads to accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced by chondrocytes, and therefore, the undegraded substrates accumulate mainly in cells and extracelluar matrix (ECM) of cartilage. This has a direct impact on cartilage and bone development, leading to systemic skeletal dysplasia. In patients with Morquio A, cartilage cells are vacuolated, and this results in abnormal chondrogenesis and/or endochondral ossification.

Areas covered: This article describes the advanced therapies of Morquio A, focused on enzyme replacement therapy (ERT) and gene therapy to deliver the drug to avascular bone lesions. ERT and gene therapies for other types of MPS are also discussed, which provide therapeutic efficacy to bone lesions.

Expert opinion: ERT, gene therapy and hematopietic stem therapy are clinically and/or experimentally conducted. However, there is no effective curative therapy for bone lesion to date. One of the limitations for Morquio A therapy is that targeting avascular cartilage tissues remains an unmet challenge. ERT or gene therapy with bone-targeting system will improve the bone pathology and skeletal manifestations more efficiently.

Keywords::

• enzyme replacement therapy
• GALNS
• gene therapy
• keratan sulfate
• mucopolysaccharidosis IVA
• tandem mass spectrometry

Acknowledgments

Editorial assistance to the manuscript was provided by Michelle Stofa at Nemours/Alfred I. duPont Hospital for Children. S Tomatsu and CJ Alméciga-Díaz regarded as joint first authors.

Notes

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