Bone marrow transplantation increases sulfatase activity in somatic tissues in a multiple sulfatase deficiency mouse model.

backgroundMultiple 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.

methodsTo test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1

resultsAfter 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1

conclusionsOur 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.