title: Treatment options for lysosomal storage disorders: developing insights.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Erasmus MC University Medical Center, Center for Lysosomal and Metabolic Diseases, Department of Paediatrics, Dr. Molewaterplein 60, Rotterdam, The Netherlands.
authors.forename: Carin M
authors.initials: CM
authors.lastname: van Gelder
authors.forename: Audrey A M
authors.initials: AA
authors.lastname: Vollebregt
authors.forename: Iris
authors.initials: I
authors.lastname: Plug
authors.forename: Ans T
authors.initials: AT
authors.lastname: van der Ploeg
authors.forename: Arnold J J
authors.initials: AJ
authors.lastname: Reuser
mesh_terms: D000818:Animals; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000503:physiopathology / Q000628:therapy*; D018832:Molecular Chaperones / Q000627:therapeutic use
chemical_list: D018832:Molecular Chaperones