Using automated patch clamp electrophysiology platforms in ion channel drug discovery: an industry perspective

ABSTRACT

Introduction

Automated patch clamp (APC) is now well established as a mature technology for ion channel drug discovery in academia, biotech and pharma companies, and in contract research organizations (CRO), for a variety of applications including channelopathy research, compound screening, target validation and cardiac safety testing.

Areas covered

Ion channels are an important class of drugged and approved drug targets. The authors present a review of the current state of ion channel drug discovery along with new and exciting developments in ion channel research involving APC. This includes topics such as native and iPSC-derived cells in ion channel drug discovery, channelopathy research, organellar and biologics in ion channel drug discovery.

Expert opinion

It is our belief that APC will continue to play a critical role in ion channel drug discovery, not only in ‘classical’ hit screening, target validation and cardiac safety testing, but extending these applications to include high throughput organellar recordings and optogenetics. In this way, with advancements in APC capabilities and applications, together with high resolution cryo-EM structures, ion channel drug discovery will be re-invigorated, leading to a growing list of ion channel ligands in clinical development.

KEYWORDS:

• Automated patch clamp
• cardiac safety
• ion channel screening
• organellar
• channelopathy
• iPS
• TMEM175
• lysosomes

Article highlights

• Automated Patch Clamp (APC) technology has become a cornerstone in ion channel drug discovery, significantly improving throughput and data quality in both academic and industrial research settings.

• APC is extensively used for ion channel target screening and cardiac safety profiling, aligning with regulatory standards such as ICH S7B and the FDA’s Comprehensive in vitro Pro-arrhythmia Assay (CiPA).

• The use of APC has been extended to include translational applications with human induced pluripotent stem (iPS) cells and native cells, bridging the gap between preclinical studies and clinical applications.

• The combination of APC functional assays with high-resolution cryo-electron microscopy (cryo-EM) structures has reinvigorated ion channel drug discovery, enabling sophisticated structure-based drug design.

• Organellar ion channels are now receiving increased attention as potential targets to treat rare and common diseases. Work is ongoing to make it possible to study intracellular ion channels with high throughput APC devices.

• Efforts are being made to integrate new techniques like optogenetics into APC platforms, potentially developing more complex and translational assays.

Declaration of interest

A Obergrussberger, N Fertig and A Kondratskyi are employed by Nanion Technologies, a provider of automated patch clamp equipment. M Rogers is a drug discovery consultant at Albion Drug Discovery Services Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.