Bone Marrow Transplantation in the Treatment of Lysosomal Storage Diseases

1990 ◽  
pp. 659-670 ◽  
Author(s):  
P. M. Hoogerbrugge ◽  
J. M. J. J. Vossen
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lysosomal Storage Diseases ◽  
Lysosomal Storage ◽  
Storage Diseases

Allogeneic bone marrow transplantation for lysosomal storage diseases

The Lancet ◽  
1995 ◽  
Vol 345 (8962) ◽  
pp. 1398-1402 ◽  
Author(s):  
P.M. Hoogerbrugge ◽  
O.F. Brouwer ◽  
P. Bordigoni ◽  
G. Cornu ◽  
P. Kapaun ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Lysosomal Storage Diseases ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Lysosomal Storage ◽  
Storage Diseases

Behavior and Therapeutic Efficacy of β-Glucuronidase–Positive Mononuclear Phagocytes in a Murine Model of Mucopolysaccharidosis Type VII

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2142-2150 ◽  
Author(s):  
Brian J. Freeman ◽  
Marie S. Roberts ◽  
Carole A. Vogler ◽  
Andrew Nicholes ◽  
A. Alex Hofling ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Therapeutic Efficacy ◽  
Lysosomal Storage Diseases ◽  
Reticuloendothelial System ◽  
Mononuclear Phagocytes ◽  
Mucopolysaccharidosis Type ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Mps Vii

Abstract Bone marrow transplantation (BMT) is relatively effective for the treatment of lysosomal storage diseases. To better understand the contribution of specific hematopoietic lineages to the efficacy of BMT, we transplanted β-glucuronidase–positive mononuclear phagocytes derived from either the peritoneum or from bone marrow in vitro into syngeneic recipients with mucopolysaccharidosis type VII (MPS VII). Cell surface marking studies indicate that the bone marrow-derived cells are less mature than the peritoneal macrophages. However, both cell types retain the ability to home to tissues rich in cells of the reticuloendothelial system after intravenous injection into MPS VII mice. The half-life of both types of donor macrophages is approximately 7 days, and some cells persist for at least 30 days. In several tissues, therapeutic levels of β-glucuronidase are present, and histopathologic analysis demonstrates that lysosomal storage is dramatically reduced in the liver and spleen. Macrophages intravenously injected into newborn MPS VII mice localize to the same tissues as adult mice but are also observed in the meninges and parenchyma of the brain. These data suggest that macrophages play a significant role in the therapeutic efficacy of BMT for lysosomal storage diseases and may have implications for treatments such as gene therapy.

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

Blood ◽  
2001 ◽  
Vol 97 (1) ◽  
pp. 327-329 ◽  
Author(s):  
Mylvaganam Jeyakumar ◽  
Francine Norflus ◽  
Cynthia J. Tifft ◽  
Mario Cortina-Borja ◽  
Terry D. Butters ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Sandhoff Disease ◽  
Lysosomal Storage ◽  
Gm2 Ganglioside ◽  
Donor Bone Marrow ◽  
The Central Nervous System ◽  
Substrate Deprivation ◽  
Hexb Gene

Abstract 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 β-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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