Mucopolysaccharidosis IVA (Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which results in the accumulation of the glycosaminoglycans (GAGs), keratan sulfate, and chondroitin-6-sulfate in the lysosomes of all tissues causing systemic dysfunction. Current treatments include enzyme replacement therapy (ERT) which can treat only certain aspects of the disease such as endurance-related biological endpoints. A key challenge in ERT is ineffective enzyme uptake in avascular tissues, which makes the treatment of the corneal, cartilage, and heart valvular tissue difficult. The aim of this study was to culture human umbilical mesenchymal stem cells (UMSC), demonstrate presence of GALNS enzyme activity within the extracellular vesicles (EVs) derived from these UMSC, and study how these secreted EVs are taken up by GALNS-deficient cells and used by the deficient cell’s lysosomes.

Mucopolysaccharidoses (MPS) are rare, inherited lysosomal storage disorders characterized by progressive multiorgan involvement. Previous studies on incidence and prevalence of MPS mainly focused on countries other than the United States (US), showing considerable variation by country. This study aimed to identify MPS incidence and prevalence in the US at a national and state level to guide clinicians and policy makers.

Mucopolysaccharidosis IVA (Morquio A disease) is a genetic disorder caused by deficiency of N-acetylgalactosamine-6-sulfate-sulfatase (GALNS), leading to accumulation of keratan sulfate and chondroitin-6-sulfate in lysosomes. Many patients become wheelchair-dependent as teens, and their life span is 20-30 years. Currently, enzyme replacement therapy (ERT) is the treatment of choice. Although it alleviates some symptoms, replacing GALNS enzyme poses several challenges including very fast clearance from circulation and instability at 37 °C. These constraints affect frequency and cost of enzyme infusion and ability to reach all tissues. In this study, we developed injectable and biodegradable polyethylene glycol (PEG) hydrogels, loaded with recombinant human GALNS (rhGALNS) to improve enzyme stability and bioavailability, and to sustain release. We established the enzyme’s release profile via bulk release experiments and determined diffusivity using fluorescence correlation spectroscopy. We observed that PEG hydrogels preserved enzyme activity during sustained release for 7 days. In the hydrogel, rhGALNS diffused almost four times slower than in buffer. We further confirmed that the enzyme was active when released from the hydrogels, by measuring its uptake in patient fibroblasts. The developed hydrogel delivery device could overcome current limits of rhGALNS replacement and improve quality of life for Morquio A patients. Encapsulated GALNS enzyme in a polyethylene glycol hydrogel improves GALNS stability by preserving its activity, and provides sustained release for a period of at least 7 days.

Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities.