Repositório Digital

A- A A+

Effects of enzyme replacement therapy started late in a murine model of mucopolysaccharidosis type I

.

Effects of enzyme replacement therapy started late in a murine model of mucopolysaccharidosis type I

Mostrar registro completo

Estatísticas

Título Effects of enzyme replacement therapy started late in a murine model of mucopolysaccharidosis type I
Autor Pasqualim, Gabriela
Baldo, Guilherme
Carvalho, Talita Giacomet de
Tavares, Angela Maria Vicente
Giugliani, Roberto
Matte, Ursula da Silveira
Abstract Mucopolysaccharidosis type I (MPS I) is a progressive disorder caused by deficiency of α- L-iduronidase (IDUA), which leads to storage of heparan and dermatan sulphate. It is suggested that early enzyme replacement therapy (ERT) leads to better outcomes, although many patients are diagnosed late and don’t receive immediate treatment. This study aims to evaluate the effects of late onset ERT in a MPS I murine model. MPS I mice received treatment from 6 to 8 months of age (ERT 6–8mo) with 1.2mg laronidase/kg every 2 weeks and were compared to 8 months-old wild-type (Normal) and untreated animals (MPS I). ERT was effective in reducing urinary and visceral GAG to normal levels. Heart GAG levels and left ventricular (LV) shortening fraction were normalized but cardiac function was not completely improved. While no significant improvements were found on aortic wall width, treatment was able to significantly reduce heart valves thickening. High variability was found in behavior tests, with treated animals presenting intermediate results between normal and affected mice, without correlation with cerebral cortex GAG levels. Cathepsin D activity in cerebral cortex also did not correlate with behavior heterogeneity. All treated animals developed anti-laronidase antibodies but no correlation was found with any parameters analyzed. However, intermediary results from locomotion parameters analyzed are in accordance with intermediary levels of heart function, cathepsin D, activated glia and reduction of TNF-α expression in the cerebral cortex. In conclusion, even if started late, ERT can have beneficial effects on many aspects of the disease and should be considered whenever possible.
Contido em PLoS ONE. San Francisco. Vol. 10, no. 2 (Feb. 2015), 15 p. e0117271
Assunto Catepsina D
Formacao de anticorpos
Mucopolissacaridose I
Origem Estrangeiro
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/143680
Arquivos Descrição Formato
000990977.pdf (4.056Mb) Texto completo (inglês) Adobe PDF Visualizar/abrir

Este item está licenciado na Creative Commons License

Este item aparece na(s) seguinte(s) coleção(ões)


Mostrar registro completo

Percorrer



  • O autor é titular dos direitos autorais dos documentos disponíveis neste repositório e é vedada, nos termos da lei, a comercialização de qualquer espécie sem sua autorização prévia.
    Projeto gráfico elaborado pelo Caixola - Clube de Criação Fabico/UFRGS Powered by DSpace software, Version 1.8.1.