Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis.
GM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal beta-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. S...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1826262687661686784 |
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| author | Elliot-Smith, E Speak, A Lloyd-Evans, E Smith, D van der Spoel, A Jeyakumar, M Butters, T Dwek, R d'Azzo, A Platt, F |
| author_facet | Elliot-Smith, E Speak, A Lloyd-Evans, E Smith, D van der Spoel, A Jeyakumar, M Butters, T Dwek, R d'Azzo, A Platt, F |
| author_sort | Elliot-Smith, E |
| collection | OXFORD |
| description | GM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal beta-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 beta-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. |
| first_indexed | 2024-03-06T19:40:01Z |
| format | Journal article |
| id | oxford-uuid:205652a2-14ab-45b6-8a66-e8005825e857 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:40:01Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:205652a2-14ab-45b6-8a66-e8005825e8572022-03-26T11:27:03ZBeneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:205652a2-14ab-45b6-8a66-e8005825e857EnglishSymplectic Elements at Oxford2008Elliot-Smith, ESpeak, ALloyd-Evans, ESmith, Dvan der Spoel, AJeyakumar, MButters, TDwek, Rd'Azzo, APlatt, FGM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal beta-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 beta-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. |
| spellingShingle | Elliot-Smith, E Speak, A Lloyd-Evans, E Smith, D van der Spoel, A Jeyakumar, M Butters, T Dwek, R d'Azzo, A Platt, F Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. |
| title | Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. |
| title_full | Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. |
| title_fullStr | Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. |
| title_full_unstemmed | Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. |
| title_short | Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. |
| title_sort | beneficial effects of substrate reduction therapy in a mouse model of gm1 gangliosidosis |
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