Small molecule drug discovery for fabry disease

Abstract

Small molecule therapy has been widely used for the treatment of a variety of diseases. Small molecule drugs can be easily administered to patients, and are advantageous in that they can cross the blood-brain barrier, do not cause autoimmune responses, and have lower manufacturing costs. In this chapter, we focus on different strategies and methods for small molecule drug development as it applies to Fabry disease. The steps involved in developing an appropriate high throughput screen to identify activators and inhibitors of alpha galactosidase A are outlined. Assay development includes optimization of the assay pH, time course, enzyme and substrate concentration and the amount of sodium taurocholate used. The assay must then be validated and confirmed using additional screens. The optimized screens can be used to identify novel lead compounds that can serve as new starting points for drug development for Fabry disease. © 2010 Springer Science+Business Media B.V.