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Oral small molecule therapy for lysosomal storage diseases

Neal J Weinreb1

  • 1University Research Foundation for Lysosomal Storage Diseases, Boca Raton, Florida 33433, USA. boneal@winning.com

Pediatric Endocrinology Reviews : PER
|January 2, 2014
PubMed

Insights

Enzyme replacement therapy (ERT) is limited for lysosomal storage disorders (LSDs). Oral small molecule drugs offer a promising alternative, potentially overcoming ERT

Area of Science:

  • Biochemistry
  • Pharmacology
  • Genetics

Background:

  • Enzyme replacement therapy (ERT) has been the standard treatment for lysosomal storage disorders (LSDs) for over two decades.
  • Current ERT approaches exhibit limitations, particularly for neuronopathic LSDs, due to poor tissue distribution, immunological intolerance, and incomplete restoration of cellular homeostasis.

Purpose of the Study:

  • To review the current landscape of small molecule therapeutics for lysosomal storage disorders.
  • To explore how small molecule drugs can overcome the limitations of traditional enzyme replacement therapy.

Main Methods:

  • Review of existing literature on small molecule drug development for LSDs.
  • Analysis of therapeutic strategies including substrate synthesis inhibition, pharmacological chaperones, and proteostasis modification.

Main Results:

  • Several oral small molecule drugs are approved or in advanced clinical trials for LSDs.
  • These drugs demonstrate potential for wide tissue distribution, including the central nervous system (CNS).
  • Approaches like substrate reduction therapy and chaperone therapy show promise in addressing LSD pathophysiology.

Conclusions:

  • Oral small molecule drugs represent a significant advancement in LSD treatment, offering potential to overcome ERT limitations.
  • Further investigation and clinical development of these agents are crucial for improving patient outcomes in LSDs.

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