title: Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts.
abstract: BACKGROUND
  Hunter syndrome, mucopolysaccharidosis type II (MPS II), is a X-linked inherited disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS), involved in the lysosomal catabolism of the glycosaminoglycans (GAG) dermatan and heparan sulfate. Such a deficiency leads to the intracellular accumulation of undegraded GAG and eventually to a progressive severe clinical pattern. Many attempts have been made in the last two to three decades to identify possible therapeutic strategies for the disorder, including gene therapy and somatic cell therapy.
  
  
  METHODS
  In this study we evaluated the intraperitoneal implantation of allogeneic myoblasts over-expressing IDS, enclosed in alginate microcapsules, in the MPS II mouse model. Animals were monitored for 8 weeks post-implantation, during which plasma and tissue IDS levels, as well as tissue and urinary GAG contents, were measured.
  
  
  CONCLUSIONS
  Induced enzyme activity occurred both in the plasma and in the different tissues analyzed. A significant decrease in urinary undegraded GAG between the fourth and the sixth week of treatment was observed. Moreover, a biochemical reduction of GAG deposits was measured 8 weeks after treatment in the liver and kidney, on average 30 and 38%, respectively, while in the spleen GAG levels were almost normalized. Finally, the therapeutic effect was confirmed by histolochemical examination of the same tissues. Such effects were obtained following implantation of about 1.5 x 10(6) recombinant cells/animal. Taken together, these results represent a clear evidence of the therapeutic efficacy of this strategy in the MPS II mouse model, and encourage further evaluation of this approach for potential treatment of human beings.
authors.affiliation: Gene Therapy Laboratory, Centre for Rare Diseases and Department of Pediatrics, University of Padova, Italy.
authors.forename: Adelaide
authors.initials: A
authors.lastname: Friso
authors.forename: Rosella
authors.initials: R
authors.lastname: Tomanin
authors.forename: Sabrina
authors.initials: S
authors.lastname: Alba
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Gasparotto
authors.forename: Elisabetta Piller
authors.initials: EP
authors.lastname: Puicher
authors.forename: Mariella
authors.initials: M
authors.lastname: Fusco
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Hortelano
authors.forename: Joseph
authors.initials: J
authors.lastname: Muenzer
authors.forename: Oriano
authors.initials: O
authors.lastname: Marin
authors.forename: Franco
authors.initials: F
authors.lastname: Zacchello
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
mesh_terms: D000818:Animals; D002214:Capsules; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016532:Mucopolysaccharidosis II / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: D002214:Capsules; D006023:Glycoproteins; D006025:Glycosaminoglycans; C018322:IDS protein, human