Gene Therapy of Sphingolipid Metabolic Disorders

Int J Mol Sci. 2023 Feb 11;24(4):3627. doi: 10.3390/ijms24043627.


Sphingolipidoses are defined as a group of rare hereditary diseases resulting from mutations in the genes encoding lysosomal enzymes. This group of lysosomal storage diseases includes more than 10 genetic disorders, including GM1-gangliosidosis, Tay-Sachs disease, Sandhoff disease, the AB variant of GM2-gangliosidosis, Fabry disease, Gaucher disease, metachromatic leukodystrophy, Krabbe disease, Niemann-Pick disease, Farber disease, etc. Enzyme deficiency results in accumulation of sphingolipids in various cell types, and the nervous system is also usually affected. There are currently no known effective methods for the treatment of sphingolipidoses; however, gene therapy seems to be a promising therapeutic variant for this group of diseases. In this review, we discuss gene therapy approaches for sphingolipidoses that are currently being investigated in clinical trials, among which adeno-associated viral vector-based approaches and transplantation of hematopoietic stem cells genetically modified with lentiviral vectors seem to be the most effective.

Keywords: AAV; LV; cell therapy; gene therapy; sphingolipid lysosomal storage diseases; sphingolipid metabolic disorders; sphingolipidosis.

Publication types

  • Review

MeSH terms

  • Gaucher Disease*
  • Genetic Therapy
  • Humans
  • Sphingolipidoses* / genetics
  • Sphingolipids / metabolism
  • Tay-Sachs Disease*


  • Sphingolipids

Grants and funding

This article has been supported by the Kazan Federal University Strategic Academic Leadership Program (PRIORITY-2030).