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

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 extende...

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Bibliographic Details
Published in:The Journal of clinical investigation 1998-05, Vol.101 (9), p.1881-1888
Main Authors: Norflus, F, Tifft, C J, McDonald, M P, Goldstein, G, Crawley, J N, Hoffmann, A, Sandhoff, K, Suzuki, K, Proia, R L
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
beta-N-Acetylhexosaminidases - deficiency
beta-N-Acetylhexosaminidases - genetics
Bone Marrow Transplantation
Brain Chemistry
Cerebral Cortex - pathology
Disease Models, Animal
Glycolipids - analysis
Longevity
Mice
Mice, Mutant Strains
Oligosaccharides - urine
Sandhoff Disease - mortality
Sandhoff Disease - therapy
Survival Analysis
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Summary: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.
ISSN:0021-9738
DOI:10.1172/jci2127