Increased Longevity and Metabolic Correction Following Syngeneic Bone Marrow Transplantation in a Murine Model of Mucopolysaccharidosis Type I

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 the glycosaminoglycans (GAG) heparan and dermatan sulfate and associated multi-systemic disease, the most severe form known as Hurler syndrome. Since 1981, the treatment of Hurler patients has often included allogeneic bone marrow transplantation (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. Since 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. Users may view, print, copy, download and text and datamine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence should be directed to: R. Scott McIvor, University of Minnesota, Minneapolis MN 55455, Telephone: 612-626-1497, Fax: 612-625-9810, ([email protected]). Conflict of interest: The authors declare that they have no competing interests. HHS Public Access Author manuscript Bone Marrow Transplant. Author manuscript; available in PMC 2015 June 14. Published in final edited form as: Bone Marrow Transplant. 2012 September ; 47(9): 1235–1240. doi:10.1038/bmt.2011.239. A uhor M anscript