Treatment options for lysosomal storage disorders: developing insights

Abstract

Introduction: Lysosomal storage disorders (LSDs) are clinically heterogeneous disorders that result primarily from lysosomal accumulation of macromolecules in various tissues. LSDs are always progressive, and often lead to severe symptoms and premature death. The identification of the underlying genetic and enzymatic defects has prompted the development of various treatment options.

Areas covered: To describe the current treatment options for LSDs, the authors provide a focused overview of their pathophysiology. They discuss the current applications and challenges of enzyme-replacement therapy, stem-cell therapy, gene therapy, chaperone therapy and substrate-reduction therapy, as well as future therapeutic prospects.

Expert opinion: Over recent decades, considerable progress has been made in the treatment of LSDs and in the outcome of patients. None of the current options are completely curative yet. They are complicated by the difficulty in efficiently targeting all affected tissues (particularly the central nervous system), in reaching sufficiently high enzyme levels in the target tissues, and by their high costs. The pathways leading from the genetic mutation to the clinical symptoms should be further elucidated, as they might prompt the development of new and ultimately curative therapies.

Keywords::

• bone marrow transplantation
• chaperone therapy
• enzyme replacement therapy
• gene therapy
• lysosomal storage disease
• lysosomal storage disorder
• stem cell transplantation
• substrate reduction therapy

Acknowledgements

The authors would like to thank W Vollebregt for layout of the illustrations and D Alexander for his critical reading of the manuscript.

Notes

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