Lysosomal storage diseases: from pathophysiology to therapy

Annu Rev Med. 2015;66:471-86. doi: 10.1146/annurev-med-122313-085916.

Abstract

Lysosomal storage diseases are a group of rare, inborn, metabolic errors characterized by deficiencies in normal lysosomal function and by intralysosomal accumulation of undegraded substrates. The past 25 years have been characterized by remarkable progress in the treatment of these diseases and by the development of multiple therapeutic approaches. These approaches include strategies aimed at increasing the residual activity of a missing enzyme (enzyme replacement therapy, hematopoietic stem cell transplantation, pharmacological chaperone therapy and gene therapy) and approaches based on reducing the flux of substrates to lysosomes. As knowledge has improved about the pathophysiology of lysosomal storage diseases, novel targets for therapy have been identified, and innovative treatment approaches are being developed.

Keywords: enzyme replacement therapy; gene therapy; pharmacological chaperone therapy; proteostasis regulators; substrate reduction therapy.

Publication types

  • Review

MeSH terms

  • Enzyme Replacement Therapy*
  • Genetic Therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lysosomal Storage Diseases / genetics
  • Lysosomal Storage Diseases / metabolism
  • Lysosomal Storage Diseases / therapy*
  • Molecular Chaperones

Substances

  • Molecular Chaperones