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Therapeutic Options for Mucopolysaccharidoses: Current and Emerging Treatments

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Abstract

Mucopolysaccharidoses (MPS) are inborn errors of metabolism produced by a deficiency of one of the enzymes involved in the degradation of glycosaminoglycans (GAGs). Although taken separately, each type is rare. As a group, MPS are relatively frequent, with an overall estimated incidence of around 1 in 20,000–25,000 births. Development of therapeutic options for MPS, including hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT), has modified the natural history of many MPS types. In spite of the improvement in some tissues and organs, significant challenges remain unsolved, including blood–brain barrier (BBB) penetration and treatment of lesions in avascular cartilage, heart valves, and corneas. Newer approaches, such as intrathecal ERT, ERT with fusion proteins to cross the BBB, gene therapy, substrate reduction therapy (SRT), chaperone therapy, and some combination of these strategies may provide better outcomes for MPS patients in the near future. As early diagnosis and early treatment are imperative to improve therapeutic efficacy, the inclusion of MPS in newborn screening programs should enhance the potential impact of treatment in reducing the morbidity associated with MPS diseases. In this review, we evaluate available treatments, including ERT and HSCT, and future treatments, such as gene therapy, SRT, and chaperone therapy, and describe the advantages and disadvantages. We also assess the current clinical endpoints and biomarkers used in clinical trials.

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Author notes

  1. Kazuki Sawamoto, Molly Stapleton, and Carlos J. Alméciga-Díaz should be regarded as joint first authors.

Authors and Affiliations

  1. Nemours Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd, Wilmington, DE, 19899-0269, USA

    Kazuki Sawamoto, Molly Stapleton & Shunji Tomatsu

  2. Department of Biological Sciences, University of Delaware, Newark, DE, USA

    Molly Stapleton

  3. Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá, DC, Colombia

    Carlos J. Alméciga-Díaz, Angela J. Espejo-Mojica, Juan Camilo Losada & Diego A. Suarez

  4. Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, DC, Colombia

    Diego A. Suarez

  5. Department of Pediatrics, Shimane University, Shimane, Japan

    Shunji Tomatsu

  6. Department of Pediatrics, Gifu University, Gifu, Japan

    Shunji Tomatsu

  7. Thomas Jefferson University, Philadelphia, PA, USA

    Shunji Tomatsu

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Correspondence to Shunji Tomatsu.

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Funding

The following funding was used to assist with the preparation of this review article: The Carol Ann Foundation, Angelo R. Cali and Mary V. Cali Family Foundation, Inc., The Vain and Harry Fish Foundation, Inc., The Bennett Foundation, Jacob Randall Foundation, Austrian and Japanese MPS Societies, Nemours Funds, Baby and Infant in Research of Health and Development to Adolescent and Young Adult from the Japan Agency for Medical Research and Development (AMED), under Grant number JP18gk0110017, an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under Grant number P30GM114736, Pontificia Universidad Javeriana (PPTA # 8275), and COLCIENCIAS (Grant ID 120380763212—PPTA # 8352).

Conflict of interest

Kazuki Sawamoto, Molly Stapleton, Carlos J. Alméciga-Díaz, Angela J. Espejo-Mojica, Juan Camilo Losada, Diego A. Suarez, and Shunji Tomatsu contributed to this review article and had no conflicts of interest with any other party.

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Sawamoto, K., Stapleton, M., Alméciga-Díaz, C.J. et al. Therapeutic Options for Mucopolysaccharidoses: Current and Emerging Treatments. Drugs 79, 1103–1134 (2019). https://doi.org/10.1007/s40265-019-01147-4

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