Transplantation of Human Umbilical Cord Blood Cells Benefits an Animal Model of Sanfilippo Syndrome Type B

Sanfilippo syndrome type B is caused by α- N -acetylglucosaminidase ( Naglu ) enzyme deficiency leading to an accumulation of undegraded heparan sulfate, a glycosaminoglycan (GAG). Cell therapy is a promising new treatment and human umbilical cord blood (hUCB) cell transplantation may be preferred for delivery of the missing enzyme. We investigated the ability of mononuclear hUCB cells administered into the lateral cerebral ventricle to ameliorate/prevent histopathological changes in mice modeling Sanfilippo syndrome type B. These are the first results supporting enzyme replacement by administered hUCB cells. In vivo , transplanted hUCB cells survived long-term (7 months), migrated into the parenchyma of the brain and peripheral organs, expressed neural antigens, and exhibited neuron and astrocyte-like morphology. Transplant benefits were also demonstrated by stable cytoarchitecture in the hippocampus and cerebellum, and by reduced GAGs in the livers of treated mutant mice. A hUCB cell transplant may be an effective therapeutic strategy for enzyme delivery in Sanfilippo syndrome type B.