Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis

Elliot-Smith, Elena, Speak, Anneliese, Lloyd-Evans, Emyr, Smith, David A., Spoel, Aarnoud C. van der, Jeyakumar, Mylvaganam, Butters, Terry, Dwek, Raymond, d'Azzo, Alessandra and Platt, Frances 2008. Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. Molecular Genetics and Metabolism 94 (2) , pp. 204-211. 10.1016/j.ymgme.2008.02.005

Full text not available from this repository.

Abstract

GM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal β-galactosidase deficiency, resulting in the storage of GM1 and GA1, primarily in the central nervous system. This disease typically afflicts infants and young children and there is currently no effective therapy. Substrate reduction therapy (SRT) could be of potential benefit.The imino sugars N-butyldeoxynojirimycin (NB-DNJ, miglustat, Zavesca™) and N-butyldeoxygalactonojirimycin (NB-DGJ) used for SRT inhibit glucosylceramide synthase (GlcCerS) that catalyses the first committed step in glycosphingolipid biosynthesis. We have compared the efficacy and tolerability of NB-DNJ and NB-DGJ in the β-galactosidase knockout mouse. NB-DGJ was better tolerated than NB-DNJ, due to intrinsic gastrointestinal tract dysfunction that was exacerbated by NB-DNJ. However, functional improvement was greatest with NB-DNJ treatment which may potentially be caused by novel anti-inflammatory properties of NB-DNJ.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Uncontrolled Keywords: GM1 gangliosidosis; lysosomal storage disease; glycosphingolipid; GM1; GA1; substrate reduction therapy; miglustat; imino sugar; N-Butyldeoxynojirimycin; N-Butyldeoxygalactonojirimycin
Publisher: Elsevier
ISSN: 1096-7192
Last Modified: 04 Jun 2017 03:22
URI: http://orca.cf.ac.uk/id/eprint/20252

Citation Data

Cited 41 times in Google Scholar. View in Google Scholar

Cited 55 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item