Emerging drugs for the treatment of mucopolysaccharidoses

ABSTRACT

Introduction: Despite being reported for the first time almost one century ago, only in the last few decades effective have treatments become available for the mucopolysaccharidoses (MPSs), a group of 11 inherited metabolic diseases that affect lysosomal function. These diseases are progressive, usually severe, and, in a significant number of cases, involve cognitive impairment.

Areas covered: This review will not cover established treatments such as bone marrow/hematopoietic stem cell transplantation and classic intravenous enzyme replacement therapy (ERT), whose long-term outcomes have already been published (MPS I, MPS II, and MPS VI), but it instead focuses on emerging therapies for MPSs. That includes intravenous ERT for MPS IVA and VII, intrathecal ERT, ERT with fusion proteins, substrate reduction therapy, gene therapy, and other novel approaches.

Expert opinion: The available treatments have resulted in improvements for several disease manifestations, but they still do not represent a cure for these diseases; thus, it is important to develop alternative methods to approach the unmet needs (i.e. bone disease, heart valve disease, corneal opacity, and central nervous system (CNS) involvement). The work in progress with novel approaches makes us confident that in 2017, when MPS will commemorate 100 years of its first report, we will be much closer to an effective cure for these challenging conditions.

KEYWORDS:

• Mucopolysaccharidoses
• lysosomal storage diseases
• glycosaminoglycans
• enzyme replacement therapy
• gene therapy
• emerging treatments

Declaration of interest

R Giugliani is principal investigator of clinical trials on MPS. He has received investigator fees, speaker honoraria, and travel grants from Amicus Therapeutics, Actelion Pharmaceuticals, BioMarin Pharmaceutical Inc, Shire, Genzyme, and Synogeva. 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 apart from those disclosed.

Acknowledgments

The authors express their gratitude to the members of the Medical Genetics Service, Gene Therapy Center, Clinical Research Group on Medical Genetics, MPS Brazil Network, and to all other groups from Hospital de Clínicas de Porto Alegre which provide support to health care, investigation, and teaching about MPSs.