Transplantation of human umbilical cord blood cells benefits an animal model of Sanfilippo syndrome type B

Sanfilippo syndrome type B is caused by alpha- 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.