Open AccessIncreased longevity and metabolic correction following syngeneic BMT in a murine model of mucopolysaccharidosis type I
Author(s) -
Daniel Wolf,
Andrew W. Lenander,
Zhenhong Nan,
Elizabeth Braunlin,
Kelly M. Podetz-Pedersen,
Chester B. Whitley,
Pankaj Gupta,
Walter C. Low,
R. Scott McIvor
Publication year - 2011
Publication title -
bone marrow transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 127
eISSN - 1476-5365
pISSN - 0268-3369
DOI - 10.1038/bmt.2011.239
Subject(s) - hurler syndrome , mucopolysaccharidosis type i , mucopolysaccharidosis i , mucopolysaccharidosis , medicine , lysosomal storage disease , dermatan sulfate , transplantation , mucopolysaccharidosis type ii , glycosaminoglycan , immunology , haematopoiesis , hunter syndrome , heparan sulfate , enzyme replacement therapy , disease , biology , stem cell , genetics , anatomy
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive inherited disease caused by deficiency of the glycosidase α-L-iduronidase (IDUA). Deficiency of IDUA leads to lysosomal accumulation of glycosaminoglycans (GAG) heparan and dermatan sulfate and associated multi-systemic disease, the most severe form of which is known as Hurler syndrome. Since 1981, the treatment of Hurler patients has often included allogeneic BMT from a matched donor. However, mouse models of the disease were not developed until 1997. To further characterize the MPS-I mouse model and to study the effectiveness of BMT in these animals, we engrafted a cohort (n=33) of 4-8-week-old Idua(-/-) animals with high levels (88.4±10.3%) of wild-type donor marrow. Engrafted animals displayed an increased lifespan, preserved cardiac function, partially restored IDUA activity in peripheral organs and decreased GAG accumulation in both peripheral organs and in the brain. However, levels of GAG and GM3 ganglioside in the brain remained elevated in comparison to unaffected animals. As these results are similar to those observed in Hurler patients following BMT, this murine-transplantation model can be used to evaluate the effects of novel, more effective methods of delivering IDUA to the brain as an adjunct to BMT.