Enzyme replacement and gene therapy for mucopolysaccharidoses: current progress and future directions

Abstract

Introduction: Mucopolysaccharidoses (MPS) are lysosomal storage disorders caused by the deficiency of enzymes that are responsible for the stepwise degradation of complex carbohydrates, the glycosaminoglycans. Whereas in the past the treatment of MPS consisted mainly of palliative care, enzyme replacement therapy (ERT) is now possible for some MPS disorders, and in the future many other therapeutic options will become available.

Areas covered: This review, based on personal experience and the currently available literature, will give an overview on the efficacy and limitations of ERT and will discuss new therapeutic approaches, such as anti-inflammatory drugs, substrate reduction therapy, chaperones and gene therapy.

Expert opinion: The therapeutic strategies available nowadays for MPS patients, namely ERT and hematopoietic stem cell transplantation, have their limitations, particularly in regard to the bone and CNS manifestation. Small molecules such as substrate inhibitors or chaperones that are capable of passing the blood–brain barrier are being developed. The use of anti-inflammatory drugs also seems to be an alternative therapeutic option. Before gene therapy can be seen as a routine treatment for MPS disorders, many issues, in particular regarding safety, have to be addressed.

Keywords:

• anti-inflammatory drugs
• chaperones
• gene therapy
• lysosomal storage disorders
• mucopolysaccharidoses
• nanoparticles
• substrate reduction
• treatment

Declaration of interest

The author has received travel support, unrestricted grants and honoraria from Shire, Genzyme, Biomarin, Actelion and Synageva. The author has not received any payment in the preparation of this manuscript and has 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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