Identification and validation of hits from high throughput screens for CFTR modulators

Abstract

These are exciting times with the appearance of small molecule compounds in clinical trials which target the basic defects caused by mutation in the CFTR gene. This progress was enabled by years of basic research probing the molecular and cellular consequences caused by mutation and the development of methods by which to study the primary anion transport defect in a high-throughput manner by robotics. Future progress with the development of new, more effective corrector compounds is needed. Such discovery will require further progress in defining the molecular targets for effective intervention using a multidisciplinary approach, merging computational, molecular, proteomic and cell biological methods. There is also an urgent need to develop means to link the right therapeutic compound to the right patients given the heterogeneity of the CF patient population. We envision a time when mid to high-throughput methods will be married with stem cell biology to enable testing a compendium of compounds on cells derived from each individual patient. Given the rate of progress in this field- this scenario may exist in the not too distant future.