Value Proposition:
The disclosed technology gives drug teams a straightforward, biology-focused way to find compounds that could help treat mood and psychotic disorders. It recreates a pathway tied to human genetic and postmortem evidence, activity-driven loss of Ankyrin‑G and related ion channel changes that disrupt how neurons fire, and produces a clear, repeatable signal (about a 50% drop in Ankyrin‑G) that can be measured in cultured brain cells. Because the assay is simple to trigger and quantify, and has been independently reproduced, it can be used to quickly screen and prioritize small molecules that prevent or reverse the harmful changes, helping to de‑risk and accelerate therapeutic development.
Unmet Need
· L-type calcium channel loci and the Ankyrin G (ANK3) locus have emerged from genome-wide association studies (GWAS) as major genetic risk factors for psychiatric disorders. Through literature reviews and research, the two gene products above are said to be linked in a signaling pathway in the cerebral cortex and forebrain structures which are relevant to psychiatric disorders. This model provides a platform to screen potential small molecule therapeutics, allowing researchers to identify compounds that restore normal neuronal function. The potential translational relevance lies in linking human genetic and postmortem findings to functional cellular phenotypes, helping prioritize promising compounds before advancing to costly animal studies or clinical trials.
Technology Description
· The disclosed technology is a primary neuron cell model designed to screen small molecules for psychiatric disorders by testing a pathway supported by genetic and postmortem evidence. In cultured mouse or rat cortical or hippocampal neurons, calcium channels are activated using KCl depolarization or a channel‑opening drug such as BayK8644, which is proposed to reduce the level of Ankyrin‑G and thereby affect sodium and potassium channels that control neuronal firing. The main readout is Ankyrin‑G levels measured by immunofluorescence, with alternative readouts including sodium or potassium channel changes or their interaction with Ankyrin‑G. The assay produces a robust, reproducible signal (about a 50% decrease in Ankyrin‑G, replicated by collaborators) and can be used to identify compounds that block or reverse these changes.
Stage of Development
· Developed
Data Availability
· N/A
Publication
