Increasing β-hexosaminidase A activity using genetically modified mesenchymal stem cells.
GM2 gangliosidosis
Sandhoff disease
Tay-Sachs disease
adeno-associated viral vectors
cell therapy
cell-mediated gene therapy
gene therapy
β-hexosaminidase
Journal
Neural regeneration research
ISSN: 1673-5374
Titre abrégé: Neural Regen Res
Pays: India
ID NLM: 101316351
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
medline:
25
7
2023
pubmed:
25
7
2023
entrez:
25
7
2023
Statut:
ppublish
Résumé
GM2 gangliosidoses are a group of autosomal-recessive lysosomal storage disorders. These diseases result from a deficiency of lysosomal enzyme β-hexosaminidase A (HexA), which is responsible for GM2 ganglioside degradation. HexA deficiency causes the accumulation of GM2-gangliosides mainly in the nervous system cells, leading to severe progressive neurodegeneration and neuroinflammation. To date, there is no treatment for these diseases. Cell-mediated gene therapy is considered a promising treatment for GM2 gangliosidoses. This study aimed to evaluate the ability of genetically modified mesenchymal stem cells (MSCs-HEXA-HEXB) to restore HexA deficiency in Tay-Sachs disease patient cells, as well as to analyze the functionality and biodistribution of MSCs in vivo. The effectiveness of HexA deficiency cross-correction was shown in mutant MSCs upon interaction with MSCs-HEXA-HEXB. The results also showed that the MSCs-HEXA-HEXB express the functionally active HexA enzyme, detectable in vivo, and intravenous injection of the cells does not cause an immune response in animals. These data suggest that genetically modified mesenchymal stem cells have the potentials to treat GM2 gangliosidoses.
Identifiants
pubmed: 37488869
pii: NeuralRegenRes_2024_19_1_212_375328
doi: 10.4103/1673-5374.375328
pmc: PMC10479847
doi:
Types de publication
Journal Article
Langues
eng
Pagination
212-219Déclaration de conflit d'intérêts
None
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