PMID- 11133779
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 97
IP  - 1
DP  - 2001 Jan 1
TI  - Enhanced survival in Sandhoff disease mice receiving a combination of substrate 
      deprivation therapy and bone marrow transplantation.
PG  - 327-9
AB  - 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.
FAU - Jeyakumar, M
AU  - Jeyakumar M
AD  - Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, 
      United Kingdom.
FAU - Norflus, F
AU  - Norflus F
FAU - Tifft, C J
AU  - Tifft CJ
FAU - Cortina-Borja, M
AU  - Cortina-Borja M
FAU - Butters, T D
AU  - Butters TD
FAU - Proia, R L
AU  - Proia RL
FAU - Perry, V H
AU  - Perry VH
FAU - Dwek, R A
AU  - Dwek RA
FAU - Platt, F M
AU  - Platt FM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glycosphingolipids)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - ADN3S497AZ (miglustat)
RN  - EC 3.2.1.52 (Hexosaminidase B)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
SB  - IM
MH  - 1-Deoxynojirimycin/*analogs & derivatives/*therapeutic use
MH  - Animals
MH  - *Bone Marrow Transplantation
MH  - Brain/metabolism
MH  - Diagnostic Techniques, Neurological
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/therapeutic use
MH  - Glycosphingolipids/metabolism
MH  - Hexosaminidase B
MH  - Mice
MH  - Sandhoff Disease/*therapy
MH  - Spinal Cord/metabolism
MH  - Survival Rate
MH  - beta-N-Acetylhexosaminidases/metabolism
EDAT- 2001/01/03 11:00
MHDA- 2001/03/03 10:01
CRDT- 2001/01/03 11:00
PHST- 2001/01/03 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2001/01/03 11:00 [entrez]
AID - S0006-4971(20)48145-5 [pii]
AID - 10.1182/blood.v97.1.327 [doi]
PST - ppublish
SO  - Blood. 2001 Jan 1;97(1):327-9. doi: 10.1182/blood.v97.1.327.