Selected Grantee Publications

Bone Marrow Transplantation Increases Sulfatase Activity in Somatic Tissues in a Multiple Sulfatase Deficiency Mouse Model

Presa et al., Communications Medicine. 2024.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11502872/pdf/43856_2024_Article_648.pdf

Multiple Sulfatase Deficiency (MSD) is a rare genetic disorder where patients demonstrate loss of function mutations in the SUMF1 gene, resulting in a severe reduction in sulfatase activity. This enzyme deficiency causes impaired lysosomal function and widespread inflammation, leading to clinical manifestations like neurodegeneration, vision and hearing loss, and cardiac disease. The researchers evaluated the therapeutic potential of hematopoietic stem cell transplant (HSCT) to initiate cross-correction, where functional sulfatase enzymes secreted from the healthy donor cells are taken up to restore function in enzyme-deficient host cells. Bone marrow from healthy male and female B6-Sumf1^(+/+) mice were transplanted into B6-Sumf1^{(S153P/S153P)} mice, a model for MSD. The results showed that HSCT is suitable to rescue sulfatase activity in peripheral organs, such as the liver, spleen, and heart, but is not beneficial alone in inhibiting the central nervous system pathology of MSD. Supported by ORIP (U54OD020351, U54OD030187, U42OD010921) and NCI.