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Enzyme replacement therapy for lysosomal diseases: lessons from 20 years of experience and remaining challenges

R J Desnick1, E H Schuchman

  • 1Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA. robert.desnick@mssm.edu

Annual Review of Genomics and Human Genetics
|September 14, 2012
PubMed

Insights

Enzyme replacement therapy (ERT) has advanced significantly for lysosomal storage diseases (LSDs) since its inception. This review highlights 20 years of ERT progress, effective principles, and ongoing challenges in treating these genetic disorders.

Area of Science:

  • Biochemistry
  • Genetics
  • Pharmacology

Background:

  • Lysosomal storage diseases (LSDs) are genetic disorders impacting cellular function.
  • Enzyme replacement therapy (ERT) was proposed in 1964 but faced significant early obstacles.
  • Overcoming challenges in enzyme production, animal models, and immune response was crucial for ERT development.

Purpose of the Study:

  • To review the historical development and progress of ERT for LSDs.
  • To emphasize key lessons learned from two decades of ERT clinical experience.
  • To outline general principles for effective ERT and identify persistent challenges.

Main Methods:

  • Historical review of ERT development for LSDs.
  • Analysis of advancements in enzyme production and gene cloning.
  • Examination of murine models and receptor-mediated targeting strategies.

Main Results:

  • ERT is now approved for six LSDs, with ongoing trials for others.
  • The first successful ERT application was for type 1 Gaucher disease in the early 1990s.
  • Significant progress has been made in overcoming initial technical and immunological hurdles.

Conclusions:

  • ERT has evolved into a viable treatment for several LSDs.
  • Understanding receptor-mediated targeting and genetic advancements has been key to ERT success.
  • Continued research is needed to address remaining challenges and expand ERT to more LSDs.

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