Document Type
Article
Publication Date
10-25-2024
Original Citation
Presa M,
Pham V,
Ray S,
Piec P,
Ryan J,
Billings T,
Coombs H,
Schlotawa L,
Lund T,
Ahrens-Nicklas R,
Lutz C.
Bone marrow transplantation increases sulfatase activity in somatic tissues in a multiple sulfatase deficiency mouse model. Commun Med (Lond). 2024;4(1):215.
Keywords
JMG
JAX Source
Commun Med (Lond). 2024;4(1):215.
ISSN
2730-664X
PMID
39448727
DOI
https://doi.org/10.1038/s43856-024-00648-y
Grant
The authors are grateful for funding and support from the United MSD Foundation (to C.L. and M.P.). This work was supported by The Center for Precision Genetics at The Jackson Laboratory (NIH grant U54 OD020351 and U54 OD030187) (to C.L.) and the Mouse Mutant Resource and Research Center (NIH grant U42 OD010921) (to C.L.)
Abstract
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: To test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1
RESULTS: After 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.