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Blood, 1 January 2001, Vol. 97, No. 1, pp. 327-329
BRIEF REPORT
Enhanced survival in Sandhoff disease mice receiving a
combination of substrate deprivation therapy and bone marrow
transplantation
Mylvaganam Jeyakumar,
Francine Norflus,
Cynthia J. Tifft,
Mario Cortina-Borja,
Terry D. Butters,
Richard L. Proia,
V. Hugh Perry,
Raymond A. Dwek, and
Frances M. Platt
From the Glycobiology Institute, Department of
Biochemistry, University of Oxford, Oxford, and the School of
Biological Sciences, University of Southampton, Southampton, United
Kingdom; and the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, Bethesda, MD.
Sandhoff disease is a lysosomal storage disorder
characterized by GM2 ganglioside accumulation in the
central nervous system (CNS) and periphery. It results from mutations
in the HEXB gene, causing a deficiency in
 -hexosaminidase. Bone marrow transplantation (BMT), which augments
enzyme levels, and substrate deprivation (using the glycosphingolipid
biosynthesis inhibitor N-butyldeoxynojirimycin [NB-DNJ]) independently have been shown to extend life
expectancy in a mouse model of Sandhoff disease. The efficacy of
combining these 2 therapies was evaluated. Sandhoff disease mice
treated with BMT and NB-DNJ survived significantly longer
than those treated with BMT or NB-DNJ alone. When the
mice were subdivided into 2 groups on the basis of their donor bone
marrow-derived CNS enzyme levels, the high enzyme group
exhibited a greater degree of synergy (25%) than the group as a whole
(13%). Combination therapy may therefore be the strategy of choice for
treating the infantile onset disease variants.
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