Encapsulated engineered myoblasts can cure Hurler syndrome

Preclinical experiments in the mouse model

E. Piller Puicher, R. Tomanin, M. Salvalaio, A. Friso, G. Hortelano, O. Marin, M. Scarpa

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mucopolysaccharidosis type I (MPSI) is an autosomic recessive, lysosomal storage disorder due to the deficit of the enzyme α-L-iduronidase (IDUA). The disease accounts for a general impairment of tissue and organ functions, mainly including heart disease, corneal clouding, organomegaly, skeletal malformations and joint stiffness. Neurological deterioration affects the severe forms. Both haemopoietic stem cell transplantation and enzyme replacement therapy can be applied to the treatment of the disorder; however, they both present several limitations. Thus, the search for alternative strategies to complement the present procedures is highly desirable. A murine myoblast cell line engineered to overexpress IDUA was generated and enclosed in alginate microcapsules, which were intra-peritoneally implanted in the MPSI mouse model. Plasma and tissue enzyme activity induced by the treatment and urinary and tissue glycosaminoglycan content were monitored in the animals, progressively sacrificed up to 4 months after implantation. Significant induction of enzyme activity and reduction of glycosaminoglycan accumulation were detected in the implanted animals, complete normalization of deposits was achieved in two animals. Intra-peritoneal implantation of alginate microcapsule confirms to be a valid approach as an endogenous enzyme replacement procedure.

Original languageEnglish
Pages (from-to)355-364
Number of pages10
JournalGene Therapy
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

Mucopolysaccharidosis I
Myoblasts
Iduronidase
Glycosaminoglycans
Capsules
Enzymes
Enzyme Replacement Therapy
Enzyme Induction
Stem Cell Transplantation
Heart Diseases
Joints
Cell Line
Therapeutics
alginic acid

Keywords

  • alginate microcapsules
  • animal model
  • Hurler syndrome
  • MPSI
  • mucopolysaccharidosis
  • somatic cell therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Piller Puicher, E., Tomanin, R., Salvalaio, M., Friso, A., Hortelano, G., Marin, O., & Scarpa, M. (2012). Encapsulated engineered myoblasts can cure Hurler syndrome: Preclinical experiments in the mouse model. Gene Therapy, 19(4), 355-364. https://doi.org/10.1038/gt.2011.94

Encapsulated engineered myoblasts can cure Hurler syndrome : Preclinical experiments in the mouse model. / Piller Puicher, E.; Tomanin, R.; Salvalaio, M.; Friso, A.; Hortelano, G.; Marin, O.; Scarpa, M.

In: Gene Therapy, Vol. 19, No. 4, 04.2012, p. 355-364.

Research output: Contribution to journalArticle

Piller Puicher, E, Tomanin, R, Salvalaio, M, Friso, A, Hortelano, G, Marin, O & Scarpa, M 2012, 'Encapsulated engineered myoblasts can cure Hurler syndrome: Preclinical experiments in the mouse model', Gene Therapy, vol. 19, no. 4, pp. 355-364. https://doi.org/10.1038/gt.2011.94
Piller Puicher, E. ; Tomanin, R. ; Salvalaio, M. ; Friso, A. ; Hortelano, G. ; Marin, O. ; Scarpa, M. / Encapsulated engineered myoblasts can cure Hurler syndrome : Preclinical experiments in the mouse model. In: Gene Therapy. 2012 ; Vol. 19, No. 4. pp. 355-364.
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