Current and new therapies for mucopolysaccharidoses

The mucopolysaccharidoses (MPSs) are a subset of lysosomal storage diseases caused by deficiencies in the enzymes required to metabolize glycosaminoglycans (GAGs), a group of extracellular heteropolysaccharides that play diverse roles in human physiology. As a result, GAGs accumulate in multiple tissues, and affected patients typically develop progressive, multisystemic symptoms in early childhood. Over the last 30 years, the treatments available for the MPSs have evolved tremendously. There are now multiple therapies that delay the progression of these debilitating disorders, although their effectiveness varies according to MPS subtype. In this review, we discuss the basic principle underlying MPS treatment (enzymatic cross correction), and we review the three general modalities currently available: hematopoietic stem cell transplantation, enzymatic replacement, and gene therapy. For each treatment type, we discuss its effectiveness across the MPS subtypes, its inherent risks, and future directions. Long term, we suspect that treatment for the MPSs will continue to evolve, and through a combination of early diagnosis and effective management, these patients will continue to live longer lives with improved outcomes for quality of life. Copyright (c) 2022, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Automated summary

The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases caused by enzyme deficiencies, leading to the accumulation of glycosaminoglycans (GAGs) in multiple tissues. Various treatment modalities, including hematopoietic stem cell transplantation, enzymatic replacement, and gene therapy, have been developed to delay disease progression. The effectiveness of these treatments varies across MPS subtypes, and future directions include early diagnosis and improved management for better patient outcomes.