Correction of murine galactosialidosis by bone marrow-derived macrophages overexpressing human protective protein/cathepsin A under control of the colony-stimulating factor-1 receptor promoter
Open accessAbstract
Galactosialidosis (GS) is a human neurodegenerative disease caused by a deficiency of lysosomal protective protein/cathepsin A (PPCA). The GS mouse model resembles the severe human condition, resulting in nephropathy, ataxia, and premature death. To rescue the disease phenotype, GS mice were transplanted with bone marrow from transgenic mice overexpressing human PPCA specifically in monocytes/macrophages under the control of the colony stimulating factor-1 receptor promoter. Transgenic macrophages infiltrated and resided in all organs and expressed PPCA at high levels. Correction occurred in hematopoietic tissues and nonhematopoietic organs, including the central nervous system. PPCA-expressing perivascular and leptomeningeal macrophages were detected throughout the brain of recipient mice, although some neuronal cells, such as Purkinje cells, continued to show storage and died. GS mice crossed into the transgenic background reflected the outcome of bone marrow-transplanted mice, but the course of neuronal degeneration was delayed in this model. These studies present definite evidence that macrophages alone can provide a source of corrective enzyme for visceral organs and may be beneficial for neuronal correction if expression levels are sufficient.
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One year post transplantation, the brain of treated mice contained numerous PPCA-positive, BM-derived repopulating microglia.
“Most importantly, 1-year post transplantation in the brain of treated mice numerous PPCA-positive, BM-derived repopulating microglia were likely responsible for the amelioration of the brain morphology and the improved motor coordination 57.”
From Galactosialidosis: historic aspects and overview of investigated and emerging treatment options (2017) · cites this paper as [57]
The Discussion reports numerous PPCA-positive perivascular and leptomeningeal macrophages one year after transplantation, not numerous repopulating microglia. The Results say PPCA expression in transplanted brains was restricted to macrophages at perivascular, leptomeningeal, and choroid plexus sites; the authors had difficulty detecting microglia and suggest BM-derived macrophages may not yet have efficiently repopulated them. No page numbers are available in our copy. (LLM, conf=0.87)
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Experimental — accuracy not yet measuredBone marrow isolated from mice with CSF-1R-driven human PPCA and transplanted into Ppca−/− mice afforded widespread correction of the systemic phenotype.
“Bone marrow isolated from these mice and transplanted into the Ppca−/− mice afforded widespread correction of the systemic phenotype, indicating that cell-specific overexpression of PPCA had sufficient therapeutic potential.”
From Galactosialidosis: historic aspects and overview of investigated and emerging treatment options (2017) · cites this paper as [57]
Overexpression of PPCA under the CSF1R promoter has restricted expression in the microglial/monocytic lineage.
“We have reported earlier that transgenic mice overexpressing PPCA under the control of the CSFR1 promoter have restricted expression of the protein in the microglial/monocytic lineage 44 .”
From Targeting Lysosomal Dysfunction to Alleviate Plaque Deposition in an Alzheimer Disease Model (2025) · cites this paper as [44]
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Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo
Hickey, W. F., & Kimura, H. (1988) · Science · doi:10.1126/science.3276004 · Cited by 1,466 · see citing works
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- [3]Rattazzi, M. C. & Dobrenis, K. (1991) in Treatment of Genetic Diseases , ed. Desnick, R. J. (Churchill Livingstone, New York), pp. 131-152.
- [7]Walkley, S. U., Thrall, M. A., Dobrenis, K., Huang, M., March, P. A., Siegel, D. A. & Wurzelmann, S. (1994) Proc. Natl. Acad. Sci. USA 91, 2970-2974.
- [15]Zhou, X. Y., Morreau, H., Rottier, R., Davis, D., Bonten, E., Gillemans, N., Wenger, D., Grosveld, F. G., Doherty, P., Suzuki, K., et al . (1995) Genes Dev. 9, 2623-2634. d'Azzo, A., Andria, G., Strisciuglio, P. & Galjaard, H. (1995) in The Metabolic and Molecular Bases of Inherited Disease , eds. Scriver, C., Beaudet, A., Sly, W. & Valle, D. (McGraw-Hill, New York), Vol. 2, pp. 2825-2838.
- [29]Perry, V. H. & Gordon, S. (1991) in International Review of Cytology: A Survey of Cell Biology , eds. Jeon, K. W. & Friedlander, M. (Academic, San Diego), Vol. 125, pp. 203-244.
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Targeting Lysosomal Dysfunction to Alleviate Plaque Deposition in an Alzheimer Disease Model
Fremuth, L. E., van de Vlekkert, D., Hu, H., Weesner, J. A., Annunziata, I., Yogalingam, G., & d’Azzo, A. (2025) · doi:10.1101/2025.04.28.651121 · Cited by 1 · see citing works
Self-citation
- Authors
- Hahn, C. N., del Pilar Martin, M., Zhou, X.-Y., Mann, L. W., & d’Azzo, A.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Department of Genetics, St. Jude Children’s Research Hospital, 332 North Lauderdale, Memphis, TN 38105
- Corresponding author
- d’Azzo, Alessandra
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-12-08
- Volume
- 95
- Issue
- 25
- Pages
- 14880-14885
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC24544
- OpenAlex
- W2013794427
- Cited by
- 56
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1 · 2013: 2
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Assisi Foundation of Memphis
- St. Jude Children's Research Hospital (CA21765)
- American Lebanese Syrian Associated Charities (CA 21765)
- National Institutes of Health (CA21765), DK-52025)
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-52025, Z01DK052025, R01DK052025)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- galactosialidosis, lysosomal storage disease, cathepsin A, bone marrow transplantation, macrophages, transgenic mice, neurodegeneration, Purkinje cells, lysosomal enzyme replacement
- MeSH terms
- Animals, Carboxypeptidases, Humans, Macrophages, Mice, Transgenic, Promoter Regions, Genetic, Genetic Therapy, Bone Marrow Transplantation, Receptor, Macrophage Colony-Stimulating Factor, Lysosomal Storage Diseases, Cathepsin A, Mice, Cell- and Tissue-Based Therapy
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