Prospective therapies for mucopolysaccharidoses

Abstract

Introduction: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficient activity of enzymes catalyzing the stepwise degradation of glycosaminoglycans (GAGs) and characterized by intra- and extralysosomal accumulation and increased excretion in urine of partially degraded GAGs, which ultimately results in cell, tissue and organ dysfunction.

Areas covered: This article provides an overview of pathophysiology, current therapeutic approaches as well as potential future treatments for MPS disorders.

Expert opinion: Therapies currently available for MPS, such as enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT) or combination of both, are not curative, but can alter the phenotype, ameliorate disease symptoms and improve survival. Their effectiveness, however, can vary considerably and complications may also occur. Several additional therapeutic strategies are now being explored, in particular, clinical trails are ongoing based on ERT with a potential to cross blood–brain barrier, substrate reduction therapy and gene therapy. Further future directions include pharmacological chaperones and stop-codon read-through technology. Treatment of MPS disorders, in particular with neuronopathic involvement, still remains a significant unmet medical need; continuous efforts are made towards the evolution of novel therapeutic strategies.

Keywords:

• chaperones
• enzyme replacement therapy
• gene therapy
• mucopolysaccharidosis
• substrate reduction therapy

Declaration of interest

A Tylki-Szymańska was involved in a multicenter open-label study evaluating safety and clinical outcomes in children aged 1.4 – 75 years with Hunter syndrome receiving idursulfase enzyme replacement therapy, which was conducted and funded by Shire. A Jurecka is currently a full-time employee of Shire. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

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