Decreased lysosomal storage in the adult MPS VII mouse brain in the vicinity of grafts of retroviral vector-corrected fibroblasts secreting high levels of β-glucuronidase

1997 ◽  
Vol 3 (7) ◽  
pp. 771-774 ◽  
Author(s):  
Rosanne M Taylor ◽  
John H Wolfe
Keyword(s):  
Mouse Brain ◽  
Retroviral Vector ◽  
Lysosomal Storage ◽  
Mps Vii

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.

scholarly journals Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 554
Author(s):  
Jeremy Wolfberg ◽  
Keerthana Chintalapati ◽  
Shunji Tomatsu ◽  
Kyoko Nagao
Keyword(s):  
Hearing Loss ◽  
Current Knowledge ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mixed Hearing Loss ◽  
Hearing Function ◽  
Common Clinical Presentation ◽  
Mps Iva ◽  
Mps Vii ◽  
Mps I

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a deficiency of one of the enzymes involved in the degradation of glycosaminoglycans. Hearing loss is a common clinical presentation in MPS. This paper reviews the literature on hearing loss for each of the seven recognized subtypes of MPS. Hearing loss was found to be common in MPS I, II, III, IVA, VI, and VII, and absent from MPS IVB and MPS IX. MPS VI presents primarily with conductive hearing loss, while the other subtypes (MPS I, MPS II, MPS III, MPS IVA, and MPS VII) can present with any type of hearing loss (conductive, sensorineural, or mixed hearing loss). The sensorineural component develops as the disease progresses, but there is no consensus on the etiology of the sensorineural component. Enzyme replacement therapy (ERT) is the most common therapy utilized for MPS, but the effects of ERT on hearing function have been inconclusive. This review highlights a need for more comprehensive and multidisciplinary research on hearing function that includes behavioral testing, objective testing, and temporal bone imaging. This information would allow for better understanding of the progression and etiology of hearing loss. Owing to the prevalence of hearing loss in MPS, early diagnosis of hearing loss and annual comprehensive audiological evaluations are recommended.

scholarly journals A retroviral vector suitable for ultrasound image-guided gene delivery to mouse brain

Gene Therapy ◽  
2011 ◽  
Vol 19 (4) ◽  
pp. 396-403 ◽  
Author(s):  
J Jang ◽  
K Yoon ◽  
D W Hwang ◽  
D S Lee ◽  
S Kim
Keyword(s):  
Gene Delivery ◽  
Mouse Brain ◽  
Ultrasound Image ◽  
Retroviral Vector ◽  
Image Guided

Neural progenitor cell engraftment corrects lysosomal storage throughout the MRS VII mouse brain

Nature ◽  
1995 ◽  
Vol 374 (6520) ◽  
pp. 367-370 ◽  
Author(s):  
Evan Y. Snyder ◽  
Rosanne M. Taylor ◽  
John H. Wolfe
Keyword(s):  
Mouse Brain ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Lysosomal Storage ◽  
Cell Engraftment

Correction of lysosomal storage in the liver and spleen of MPS VII mice by implantation of genetically modified skin fibroblasts

1993 ◽  
Vol 4 (2) ◽  
pp. 154-159 ◽  
Author(s):  
Philippe Moullier ◽  
Delphine Bohl ◽  
Jean-Michel Heard ◽  
Olivier Danos
Keyword(s):  
Genetically Modified ◽  
Skin Fibroblasts ◽  
Lysosomal Storage ◽  
Mps Vii

In utero transplantation of fetal liver cells in the mucopolysaccharidosis type VII mouse results in low-level chimerism, but overexpression of β-glucuronidase can delay onset of clinical signs

Blood ◽  
2001 ◽  
Vol 97 (6) ◽  
pp. 1625-1634 ◽  
Author(s):  
Margret L. Casal ◽  
John H. Wolfe
Keyword(s):  
Stem Cells ◽  
Gene Transfer ◽  
Progenitor Cells ◽  
Fetal Liver ◽  
Retroviral Vector ◽  
In Utero ◽  
Hematopoietic Stem ◽  
Donor Cells ◽  
Stem And Progenitor Cells ◽  
Mps Vii

Mice with the lysosomal storage disease mucopolysaccharidosis (MPS) VII, caused by a deficiency of β-glucuronidase (GUSB), have signs of disease present at birth. Bone marrow transplantation (BMT) or retroviral vector–mediated gene transfer into hematopoietic stem cells can partially correct the disease in adult mice, and BMT performed at birth results in a better clinical outcome. Thus, treatment in utero may result in further improvement. However, this must be done without cyto-ablation, and the donor cells do not have a competitive repopulating advantage over host cells. Transplantation in utero of either syngeneic fetal liver hematopoietic stem cells marked with a retroviral vector, or allogeneic donor cells that constitutively express high levels of human GUSB from a transgene, resulted in only about 0.1% engraftment in the adult. Immuno-affinity enrichment of stem and progenitor cells of 5- to 10-fold resulted in significantly higher GUSB activities at 2 months of age, but by 6 months engraftment was about 0.1%. Attempts to further increase the number of stem and progenitor cells were deleterious to the recipients. Nevertheless, GUSB expressed during the first 2 months of life in MPS VII fetuses could delay the onset of overt signs of disease. This suggests that the expression of some normal enzyme activity beginning in fetal life may offer the possibility of slowing the progression of the disease until more definitive postnatal transplantation or gene transfer to stem cells could be accomplished.

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