KV3.1 is a voltage-gated potassium channel encoded by the KCNC1 gene. Mutations in the KV3.1 protein can manifest as a variety of neurological disorders including myoclonic epilepsy and ataxia due to K+ channel mutation (MEAK), developmental epileptic encephalopathy (DEE), or hypotonia.
The KCNC1 Foundation was founded by the parents of Eliana, a child from Canada who was diagnosed with an ultra-rare de novo mutation (V434L) in the KCNC1 gene, which encodes the KV3.1 ion channel in humans, at age 9 months. Eliana does not display typical DEE, but exhibits significant hypotonia, cortical-visual impairment, vertical nystagmus, and global delays. The KCNC1 Foundation has registered 36 patients affected by 14 different genetic variants in the KCNC1 gene. Of these patients, 25% share the A421V variant, 12.5% have MEAK caused by the R320H variant, a few exhibit the V432M variant, and the remaining variants are seen in 1 – 3 patients.
Development of a robust hNaV1.9 high-throughput screening assay on the Sophion Qube384 platform. This is complemented by a suite of ion channel selectivity assays and sensory neuron recordings to create a versatile screening cascade to support NaV1.9 drug discovery programmes.
Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.