Enzyme Replacement Therapy with Elosulfase alfa for Mucopolysaccharidosis IVA (Morquio A Syndrome): Milestones and Challenges

@article{Puckett2017EnzymeRT,
  title={Enzyme Replacement Therapy with Elosulfase alfa for Mucopolysaccharidosis IVA (Morquio A Syndrome): Milestones and Challenges},
  author={Y. Puckett and H. Mulinder and A. Monta{\~n}o},
  journal={Expert Opinion on Orphan Drugs},
  year={2017},
  volume={5},
  pages={741 - 752}
}
ABSTRACT Introduction: Mucopolysaccharidosis IVA (Morquio A syndrome) is an inherited, autosomal recessive disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which results in excessive lysosomal storage of keratan sulfate and chondroitin-6-sulfate in many tissues and organs. This accumulation causes a systemic skeletal dysplasia and leads to multiple clinical manifestations, including impaired endurance and respiratory function. Elosulfase alfa (trade name… Expand
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Mucopolysaccharidoses (MPS) are a group of genetic diseases that are caused by deficient lysosomal enzymes involved in the breakdown of glycosaminoglycans (GAGs), resulting in the accumulation ofExpand
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Intravenous weekly infusions of recombinant enzymes for MPS I, II, IVA, VI, and VII have proven to be safe and efficacious for somatic symptoms, and ERT has been shown to decrease urinary glycosaminoglycan levels and organomegaly, while improving stamina of patients, respiratory function, and quality of life. Expand
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Using an immunodominant peptide or the complete enzyme to orally induce tolerance to GALNS prior to ERT, resulted in several improvements to ERTs in mice, which could be extrapolated to other lysosomal storage disorders where immune response hinders ERT. Expand
Characterization of Human Recombinant N-Acetylgalactosamine-6-Sulfate Sulfatase Produced in Pichia pastoris as Potential Enzyme for Mucopolysaccharidosis IVA Treatment.
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The production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme, represents an important step in the development of a P. pastoris-based platform for production of a therapeutic GAL NS for MPS IVA enzyme replacement therapy. Expand
Effect of enzyme replacement therapy on the growth of patients with Morquio A
TLDR
Overall, ERT-treated patients do not experience growth improvement and continue to exhibit poor growth despite early ERT intervention before 5 years of age, indicating that current intravenous ERT is ineffective at correcting abnormal growth in MPS IVA. Expand
Umbilical mesenchymal stem cell-derived extracellular vesicles as enzyme delivery vehicle to treat Morquio A fibroblasts
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This enzyme delivery method, which was unaffected by M6P inhibition, can function as a novel technique for reducing GAG accumulation in cells in avascular tissues, thereby providing a potential treatment option for Morquio A syndrome. Expand
Biodegradable polyethylene glycol hydrogels for sustained release and enhanced stability of rhGALNS enzyme
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The developed hydrogel delivery device could overcome current limits of rhGALNS replacement and improve quality of life for Morquio A patients by preserving its activity, and provides sustained release for a period of at least 7 days. Expand
Tailoring the AAV2 capsid vector for bone-targeting
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