title: Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice.
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.
authors.affiliation: Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: F
authors.initials: F
authors.lastname: Norflus
authors.forename: C J
authors.initials: CJ
authors.lastname: Tifft
authors.forename: M P
authors.initials: MP
authors.lastname: McDonald
authors.forename: G
authors.initials: G
authors.lastname: Goldstein
authors.forename: J N
authors.initials: JN
authors.lastname: Crawley
authors.forename: A
authors.initials: A
authors.lastname: Hoffmann
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D016026:Bone Marrow Transplantation; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D006017:Glycolipids / Q000032:analysis; D008136:Longevity; D051379:Mice; D008817:Mice, Mutant Strains; D009844:Oligosaccharides / Q000652:urine; D012497:Sandhoff Disease / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency* / Q000235:genetics
chemical_list: D006017:Glycolipids; D009844:Oligosaccharides; D001619:beta-N-Acetylhexosaminidases