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

Francine Norflus, Cynthia J. Tifft, Michael P. McDonald, Gregory Goldstein, Jacqueline Crawley, Alexander Hoffmann, Konrad Sandhoff, Kinuko Suzuki, Richard L. Proia

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The G(M2) gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the G(M2) 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 ~ 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 β-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 β-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 G(M2) gangliosidoses.

Original languageEnglish (US)
Pages (from-to)1881-1888
Number of pages8
JournalJournal of Clinical Investigation
Volume101
Issue number9
StatePublished - May 1 1998
Externally publishedYes

Keywords

  • Beta-N- acetylhexosaminidase/metabolism
  • Blood-brain barrier
  • Disease models, animal
  • Gangliosidoses/physiopathology
  • Tay-Sachs disease/metabolism

ASJC Scopus subject areas

  • Medicine(all)

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