Bone marrow transplantation increases sulfatase activity in somatic tissues in a multiple sulfatase deficiency mouse model.
Journal
Communications medicine
ISSN: 2730-664X
Titre abrégé: Commun Med (Lond)
Pays: England
ID NLM: 9918250414506676
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
28
10
2023
accepted:
16
10
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Multiple Sulfatase Deficiency (MSD) is an ultra-rare autosomal recessive disorder characterized by deficient enzymatic activity of all known sulfatases. MSD patients frequently carry two loss of function mutations in the SUMF1 gene, encoding a formylglycine-generating enzyme (FGE) that activates 17 different sulfatases. MSD patients show common features of other lysosomal diseases like mucopolysaccharidosis and metachromatic leukodystrophy, including neurologic impairments, developmental delay, and visceromegaly. There are currently no approved therapies for MSD patients. Hematopoietic stem cell transplant (HSCT) has been applied with success in the treatment of certain lysosomal diseases. In HSCT, donor-derived myeloid cells are a continuous source of active sulfatase enzymes that can be taken up by sulfatase-deficient host cells. Thus, HSCT could be a potential approach for the treatment of MSD. To test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1 After 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1 Our results indicate that HSCT could be a suitable approach to treat MSD-pathology affecting peripheral organs, however that benefit to CNS pathology might be limited. Multiple Sulfatase Deficiency (MSD) is a rare genetic disorder caused by loss-of-function variations in the SUMF1 gene. This deficiency results in the accumulation of toxic compounds, leading to developmental delays and neurological impairments. In a bone marrow transplant (BMT), donor cells are infused into the patient and secrete active proteins that can help remove those toxic compounds. We carried out BMT in a mouse model for MSD and saw beneficial effects on peripheral organs, such as the liver and heart, but less change in neurological symptoms. Our results will be useful for the design of potential cell therapy approaches that could be used clinically to treat MSD.
Sections du résumé
BACKGROUND
BACKGROUND
Multiple Sulfatase Deficiency (MSD) is an ultra-rare autosomal recessive disorder characterized by deficient enzymatic activity of all known sulfatases. MSD patients frequently carry two loss of function mutations in the SUMF1 gene, encoding a formylglycine-generating enzyme (FGE) that activates 17 different sulfatases. MSD patients show common features of other lysosomal diseases like mucopolysaccharidosis and metachromatic leukodystrophy, including neurologic impairments, developmental delay, and visceromegaly. There are currently no approved therapies for MSD patients. Hematopoietic stem cell transplant (HSCT) has been applied with success in the treatment of certain lysosomal diseases. In HSCT, donor-derived myeloid cells are a continuous source of active sulfatase enzymes that can be taken up by sulfatase-deficient host cells. Thus, HSCT could be a potential approach for the treatment of MSD.
METHODS
METHODS
To test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1
RESULTS
RESULTS
After 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1
CONCLUSIONS
CONCLUSIONS
Our results indicate that HSCT could be a suitable approach to treat MSD-pathology affecting peripheral organs, however that benefit to CNS pathology might be limited.
Multiple Sulfatase Deficiency (MSD) is a rare genetic disorder caused by loss-of-function variations in the SUMF1 gene. This deficiency results in the accumulation of toxic compounds, leading to developmental delays and neurological impairments. In a bone marrow transplant (BMT), donor cells are infused into the patient and secrete active proteins that can help remove those toxic compounds. We carried out BMT in a mouse model for MSD and saw beneficial effects on peripheral organs, such as the liver and heart, but less change in neurological symptoms. Our results will be useful for the design of potential cell therapy approaches that could be used clinically to treat MSD.
Autres résumés
Type: plain-language-summary
(eng)
Multiple Sulfatase Deficiency (MSD) is a rare genetic disorder caused by loss-of-function variations in the SUMF1 gene. This deficiency results in the accumulation of toxic compounds, leading to developmental delays and neurological impairments. In a bone marrow transplant (BMT), donor cells are infused into the patient and secrete active proteins that can help remove those toxic compounds. We carried out BMT in a mouse model for MSD and saw beneficial effects on peripheral organs, such as the liver and heart, but less change in neurological symptoms. Our results will be useful for the design of potential cell therapy approaches that could be used clinically to treat MSD.
Identifiants
pubmed: 39448727
doi: 10.1038/s43856-024-00648-y
pii: 10.1038/s43856-024-00648-y
doi:
Types de publication
Journal Article
Langues
eng
Pagination
215Informations de copyright
© 2024. The Author(s).
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