Utilizing structural insights of ion channels to develop new pharmacological strategies to target conditions like arrhythmia and epilepsy

About 300,000 and 80,000 Swedes suffer from cardiac arrhythmias or epilepsy, respectively.

Up to 30% of affected individuals do not respond well to current treatment, which causes an immense burden on individuals and society and highlight the urgent need for new treatments.

Although voltage-gated potassium (Kv) channels are promising new pharmacological targets to treat such conditions, a major hurdle in drug development is the challenge of developing selective drug molecules.

This project utilizes front-line experimental and computational approaches and the diverse Kv7 family, implicated in arrhythmia and epilepsy with atomic structures recently solved, to exploit new conceptual strategies to address the outstanding need of effective and selective Kv channel modulators.

We aim to: (i) elucidate selectivity mechanisms of endogenous Kv7 modulators, to exploit natural solutions to drug design, (ii) develop synthetic Kv7 modulators that target unique protein surfaces, to allow for rational design of selective compounds, and (iii) assess promising lead modulators in other cell systems and on a panel of ion channels, to evaluate translational potential.

The successful completion of the proposed project would significantly advance our understanding of how to target Kv7 channels with new classes of drug molecule using new druggable sites and selectivity mechanisms, which ultimately will open up new pharmacological avenues.