Recombinant encapsulated cells overexpressing alpha-L-iduronidase correct enzyme deficiency in human mucopolysaccharidosis type I cells. 2012

Guilherme Baldo, and Fabiana Quoos Mayer, and Maira Burin, and Joaquín Carrillo-Farga, and Ursula Matte, and Roberto Giugliani
Gene Therapy Center, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.

Mucopolysaccharidosis I (MPS I) is an autosomal recessive lysosomal storage disease due to deficient α-L-iduronidase (IDUA) activity. It results in the accumulation of the glycosaminoglycans (GAGs) heparan and dermatan sulfate and leads to several clinical manifestations. Available treatments are limited in their efficacy to treat some aspects of the disease. Thus, new approaches have been studied for the treatment of MPS I. Here, we tested the ability of recombinant baby hamster kidney cells transfected with human IDUA cDNA in correcting skin fibroblasts from MPS I patients in vitro. Our results showed an increase in IDUA activity in MPS I fibroblasts after 15, 30 and 45 days of coculture with the capsules. Cytological analysis showed a marked reduction in GAG storage within MPS I cells. Enzyme uptake by the fibroblasts was blocked in a dose-dependent manner with mannose-6-phosphate (M6P), indicating that cells use the M6P receptor to internalize the recombinant enzyme. Capsules were effective in correcting MPS I cells even after a 12-month period of cryopreservation. Taken together, our results indicate that cell encapsulation is a potential approach for treatment of MPS I. This approach becomes particularly interesting as a complementary approach, since the capsules could be implanted in sites which current treatments available are not able to reach. Future studies will focus on the efficacy of this approach in vivo.

UI MeSH Term Description Entries
D007068 Iduronidase An enzyme that hydrolyzes iduronosidic linkages in desulfated dermatan. Deficiency of this enzyme produces Hurler's syndrome. EC 3.2.1.76. alpha-L-Idosiduronase,alpha-L-Iduronidase,alpha L Idosiduronase,alpha L Iduronidase
D008059 Mucopolysaccharidosis I Systemic lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDURONIDASE) and characterized by progressive physical deterioration with urinary excretion of DERMATAN SULFATE and HEPARAN SULFATE. There are three recognized phenotypes representing a spectrum of clinical severity from severe to mild: Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome (formerly mucopolysaccharidosis V). Symptoms may include DWARFISM; hepatosplenomegaly; thick, coarse facial features with low nasal bridge; corneal clouding; cardiac complications; and noisy breathing. Hurler's Syndrome,Hurler-Scheie Syndrome,Lipochondrodystrophy,Mucopolysaccharidosis V,Pfaundler-Hurler Syndrome,Scheie's Syndrome,Gargoylism,Gargoylism, Hurler Syndrome,Hurler Disease,Hurler Syndrome,Hurler's Disease,Mucopolysaccharidosis 1,Mucopolysaccharidosis 5,Mucopolysaccharidosis I-S,Mucopolysaccharidosis Type I,Mucopolysaccharidosis Type Ih,Mucopolysaccharidosis Type Ih S,Mucopolysaccharidosis Type Is,Scheie Syndrome,alpha-L-Iduronidase Deficiency,Disease, Hurler's,Gargoylisms,Hurler Scheie Syndrome,Hurler Syndrome Gargoylism,Lipochondrodystrophies,Mucopolysaccharidosis I S,Mucopolysaccharidosis Is,Mucopolysaccharidosis Type Ihs,Syndrome, Hurler's,Syndrome, Scheie's,Type Ih, Mucopolysaccharidosis,Type Ihs, Mucopolysaccharidosis,alpha L Iduronidase Deficiency,alpha-L-Iduronidase Deficiencies
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002214 Capsules Hard or soft soluble containers used for the oral administration of medicine. Capsule,Microcapsule,Microcapsules
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006025 Glycosaminoglycans Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine (see ACETYLGLUCOSAMINE) or N-acetylgalactosamine (see ACETYLGALACTOSAMINE). Glycosaminoglycan,Mucopolysaccharides
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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