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Glycosphingolipid lysosomal storage diseases: therapy and pathogenesis

M Jeyakumar1, T D Butters, R A Dwek

  • 1Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, UK.

Neuropathology and Applied Neurobiology
|October 9, 2002
PubMed

Insights

Mouse models reveal insights into the pathogenesis of glycosphingolipidoses, a group of paediatric neurodegenerative diseases caused by enzyme defects in glycosphingolipid (GSL) breakdown. These models aid in developing new therapeutic strategies.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Genetics

Background:

  • Paediatric neurodegenerative diseases, known as glycosphingolipidoses, stem from genetic defects in glycosphingolipid (GSL) metabolism.
  • These disorders involve lysosomal accumulation of GSL substrates, particularly impacting the central nervous system (CNS).
  • Current understanding of disease mechanisms and therapeutic options for these conditions remains limited.

Purpose of the Study:

  • To review the insights gained from mouse models regarding the pathogenesis of glycosphingolipidoses.
  • To discuss the progress in evaluating experimental therapies for these neurodegenerative disorders using animal models.

Main Methods:

  • Utilizing genetically engineered mouse models that mimic human glycosphingolipidoses.
  • Analyzing lysosomal storage, GSL substrate accumulation, and neuroinflammation in affected mouse models.
  • Evaluating the efficacy of various experimental therapeutic interventions in these mouse models.

Main Results:

  • Mouse models have elucidated key pathogenic pathways, including GSL accumulation and subsequent neurodegeneration.
  • These models demonstrate the utility of studying enzyme deficiencies in GSL catabolism.
  • Progress has been made in assessing the potential of novel therapeutic approaches, such as enzyme replacement and gene therapy, in preclinical settings.

Conclusions:

  • Mouse models are invaluable tools for understanding the complex pathogenesis of paediatric glycosphingolipidoses.
  • These models are crucial for advancing the development and preclinical evaluation of effective therapies for these devastating neurodegenerative diseases.

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