Membrane Assays, Inc. (MAI) seeks to develop and commercialize a high throughput screening (HTS) assay for voltage-gated ion channel targets. The assay is called the Ion Channel Assay (ICA). The ICA uses an electric field to stimulate voltage-gated ion channels. The cellular response is detected optically using fluorescence technology. The ICA is an enhanced 96-well microwell plate. On the bottom surface of each of the 96 wells are microelectrodes. Cells grown on the bottom of the well make electrical contact with the microelectrodes. When a voltage is applied between the electrodes, the local electrical potential across the cellular membrane is altered triggering a response by the voltage-gated ion channels. The action of a pharmaceutical to block, increase or decrease this response can then be measured. Voltage-gated ion channels play a critical role in such biological processes as the beating of the human heart, the contraction of muscles, and the release of hormones. Therefore, these channels are also important drug targets. No effective manner of rapidly testing the action of a pharmaceutical against a voltage-gated ion channel exists. Traditional patch clamping is too slow and even the new automated patch clamp products, currently in beta testing, do not have the throughput required. The result is missed good drugs. In addition, unknown side-effects of pharmaceuticals on a particular voltage-gated ion channel in the heart, the hERG channel, have led to the removal of 5 drugs from U.S. market. Thus, even if the target molecular of a pharmaceutical is not a voltage-gated ion channel potential new drugs must still be tested against a voltage-gated ion channel, the hERG channel, to uncover side-effects. MAI proposes to develop a critically needed HTS assay for voltage-gated ion channel targets. The assay is easy to use and compatible with equipment currently in place at most large pharmaceutical companies. Phase I funds will be used to manufacture 100, 96-well plate devices. The fabrication of these first 100 devices will verify the technical feasibility of the proposed manufacturing process and provide plates for ongoing biological testing and assay development. Electrical testing will also be performed.
