Hurler Syndrome or Mucopolysaccharidosis I (MPS I) is an autosomal recessive lysosomal storage
disease characterized by skeletal abnormalities, hepatosplenomegaly, and neurological degeneration.
Children who exhibit MPS I lack α-L-iduronidase (IDUA), a crucial enzyme in the degradation pathway
of glycosaminoglycans (GAGs), specifically heparan and dermatan sulfate. GAG accumulation in
lysosomes interferes with normal cell function creating multi-systemic problems. Current treatments
including enzyme replacement therapy and hematopoietic stem cell transplantation are not widely
available and fail to correct the majority of symptoms, particularly mental retardation and skeletal
anomalies. Using a NOD/SCID immunodeficient mouse model of MPS I, we attempted to correct the
enzyme deficiency by transplanting human multipotent adult progenitor cells (MAPCs) directly into the
striatum within five days of birth. Through the process of cross-correction, the IDUA enzyme released
from the transplanted cells is taken up by the defective cells. The efficacy of the MAPCs was
investigated through measurement of IDUA levels in different tissues, immunohistochemical staining,
and sensorimotor testing. The transplanted MAPCs were detected throughout the central nervous
system along with decreased levels of GAGs indicating sufficient delivery of IDUA to the cells.
Sensorimotor coordination on a rotarod test improved in the MAPC-treated MPS I mice compared to
untreated MPS I mice. These results denote that transplantation of MAPCs into the striatum greatly
reduces GAG tissue levels in the brain and ameliorates sensorimotor function in MPS I mice.
Additional contributors: Zhenhong Nan; Laurie Shekel; Matthew S. Nelson; Shaukat A. Kahn; Oleg Ryabinin; Pankaj Gupta; Walter C. Low (faculty mentor).
Correction of Mucopolysaccharidosis Type I (MPS I) with Multipotent Adult Progenitor Cells (MAPCs) in an Immunodeficient Mouse Model.
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