title: Substrate reduction therapy in mouse models of the glycosphingolipidoses.
abstract: Substrate reduction therapy uses small molecules to slow the rate of glycolipid biosynthesis. One of these drugs, N-butyldeoxynojirimycin (NB-DNJ), shows efficacy in mouse models of Tay-Sachs, Sandhoff and Fabry diseases. This offers the prospect that NB-DNJ may be of therapeutic benefit, at least in the juvenile and adult onset variants of these disorders. The infantile onset variants will require an additional enzyme-augmenting modality if the pathology is to be significantly improved. A second drug, N-butyldeoxyglactonojirimycin, looks very promising for treating storage diseases with neurological involvement as high systemic dosing is achievable without any side-effects.
authors.affiliation: Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. fran@glycob.ox.ac.uk
authors.forename: Frances M
authors.initials: FM
authors.lastname: Platt
authors.forename: Mylvaganam
authors.initials: M
authors.lastname: Jeyakumar
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.forename: Tanya
authors.initials: T
authors.lastname: Heare
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Terry D
authors.initials: TD
authors.lastname: Butters
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D013106:Sphingolipidoses / Q000188:drug therapy* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat