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. 1998 May 1;101(9):1881–1888. doi: 10.1172/JCI2127

Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice.

F Norflus 1, C J Tifft 1, M P McDonald 1, G Goldstein 1, J N Crawley 1, A Hoffmann 1, K Sandhoff 1, K Suzuki 1, R L Proia 1
PMCID: PMC508774  PMID: 9576752

Abstract

The GM2 gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the GM2 activator deficiency. Bone marrow transplantation (BMT) was examined as a potential treatment for these disorders using a Sandhoff disease mouse model. BMT extended the life span of these mice from approximately 4.5 mo to up to 8 mo and slowed their neurologic deterioration. BMT also corrected biochemical deficiencies in somatic tissues as indicated by decreased excretion of urinary oligosaccharides, and lower glycolipid storage and increased levels of beta-hexosaminidase activity in visceral organs. Even with neurologic improvement, neither clear reduction of brain glycolipid storage nor improvement in neuronal pathology could be detected, suggesting a complex pathogenic mechanism. Histological analysis revealed beta-hexosaminidase-positive cells in the central nervous system and visceral organs with a concomitant reduction of colloidal iron-positive macrophages. These results may be important for the design of treatment approaches for the GM2 gangliosidoses.

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Selected References

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