Substrate reduction therapy in mouse models of the glycosphingolipidoses.

Journal article

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: Platt, F; Jeyakumar, M; Andersson, U; Heare, T; Dwek, R

• Publication status: Published
• Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• Volume: 358
• Issue: 1433
• Pages: 947-954
• Publication date: 2003-05-01
• DOI: 10.1098/rstb.2003.1279
• EISSN: 1471-2970
• ISSN: 0962-8436
• Language: English
• Keywords: 1-Deoxynojirimycin; Substrate Specificity; Disease Models, Animal; Animals; Sphingolipidoses; Enzyme Inhibitors; Mice