Substrate reduction therapy in mouse models of the glycosphingolipidoses.
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.
Platt
Frances M
FM
Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. fran@glycob.ox.ac.uk
Jeyakumar
Mylvaganam
M
Andersson
Ulrika
U
Heare
Tanya
T
Dwek
Raymond A
RA
Butters
Terry D
TD
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
D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat