Automated patch-clamp assay for a “putative” ion channel: APOL1

Apolipoprotein L1 (APOL1) is a human serum protein conferring resistance to African trypanosomes by forming a cation-selective Na⁺-K⁺ channel, but additionally, it has been reported to conduct Ca²⁺. Variants of APOL1, G1 and G2 have been linked to Chronic Kidney Disease (CKD). CKD affects approximately 37 million people in the U.S., with more than 700,000 patients suffering from end-stage renal disease (ESRD) that may require chronic dialysis. Despite a strong association between APOL1 variants and risk of kidney disease, the underlying mechanism for potential kidney damage is not well-understood.

Accordingly, there are currently no approved therapies that address APOL1-associated CKD, and individuals with APOL1 risk variants with CKD represent a significant unmet medical need. Consequently, the search for APOL1 modulators remains challenging but crucial.

Here, we present data collected on the QPatch showing the development of an assay for APOL1 from construct generation to adaptation to an automated patch clamp system.