Automated Patch Clamp in Cystic Fibrosis Drug Discovery

In October 2020, Enterprise Therapeutics’ TMEM16A programme was acquired by Roche/Genentech. This acquisition was the culmination of a research and discovery journey initiated by Enterprise Therapeutics in 2014, with the goal of providing a novel treatment paradigm suitable for patients with cystic fibrosis and other muco-obstructive diseases. This journey also highlights the enormous technological progress that has developed in the performance and capabilities of Automated Patch Clamp (APC) platforms in the past two decades.

The direct measurements of ion channel activity and accurate control of channel gating parameters that APC systems provide, proved pivotal in hit finding, hit triage and rapid lead compound optimization (Danahay et al. 2020). In this whitepaper, we highlight how APC was instrumental in the success of the TMEM16A programme.

Using this case study, we show how the development of APC systems in the past decade is opening up a new era of drug discovery, providing tools for both high throughput and high-quality ion channel recordings. Consequently, APC gives researchers the capability to advance their drug discovery on ion channels, allowing faster definition and screening of these critical disease targets, leading to wide, new investigative vistas in developing much-needed novel treatments.

Keywords: Cystic fibrosis, CFTR