Therapies of mucopolysaccharidosis type IV A (Morquio syndrome type A)

Introduction: Morquio syndrome type A, is one of the lysosomal diseases, and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme leads to accumulation of glycosaminoglycans (GAG), 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 syndrome type A, cartilage cells are vacuolated and this results in abnormal chondrogenesis and/or endochondral ossification.

Areas covered: We will describe advanced therapies of Morquio syndrome type A, focused on ERT and gene therapy to deliver the drug to avascular bone lesions. We also review ERT and gene therapies for other types of MPS, which provide therapeutic efficacy to bone lesions.

Expert opinion: Enzyme replacement therapy (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 therapy for Morquio syndrome type A 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.