Workpackage 4

Substrate reduction therapy

Leader of the WP is Timothy Cox from the University of Cambridge (Cambridge, UK).

WP4 is designed to enhance understanding and applicability of substrate inhibition (substrate reduction therapy, SRT) to human lysosomal diseases with reference to two main classes: the glycospingolipidoses and the mucopolysaccharidoses.

The objectives of WP4 are:

1. To improve the understanding of the mechanism of action of iminosugars and morpholino compounds in Gaucher disease (GD) with a particular focus on possible effects of the trafficking of glycosphingolipids, cytokine release and non-specific immunosuppressive effects.

2. To test whether the combination of arylsulphatase B (ARSB) gene transfer and SRT obtained with rhodamine B is more therapeutically relevant than each of the two strategies alone.