Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation.

Journal article

Sandhoff disease is a lysosomal storage disorder characterized by G(M2) ganglioside accumulation in the central nervous system (CNS) and periphery. It results from mutations in the HEXB gene, causing a deficiency in beta-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.

Authors: Jeyakumar, M; Norflus, F; Tifft, C; Cortina-Borja, M; Butters, T

• Publication status: Published
• Journal: Blood
• Volume: 97
• Issue: 1
• Pages: 327-329
• Publication date: 2001-01-01
• DOI: 10.1182/blood.v97.1.327
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Brain; Diagnostic Techniques, Neurological; Animals; Survival Rate; beta-N-Acetylhexosaminidases; Sandhoff Disease; 1-Deoxynojirimycin; Glycosphingolipids; Enzyme Inhibitors; Bone Marrow Transplantation; Mice; Disease Models, Animal; Hexosaminidase B; Spinal Cord