Cell-based high-throughput screen for cognitive-enhancing drugs

Development of drugs to treat dementia and other cognitive disorders has been slow, in large part because of the lack of rapid, efficient means to screen compound libraries for promising leads. We are developing a high-throughput screen to meet this need. The assay is based upon the ability of brain cells in culture to undergo long-term potentiation (LTP), an activity-dependent change in the strength of their electrical connections that is closely related to memory formation in the brain. Compounds that enhance LTP are likely candidates for memory-enhancing drugs. We have combined chemical induction of LTP with optical readout of its magnitude, via expression of LTP-associated gene products, to yield a robust assay suitable for scale-up and automation. The assay has already successfully identified LTP-enhancing compounds. With appropriate modifications, the approach can be easily extended to screen for drugs modulating a variety of other important neurological and non-neurological conditions associated with changes in gene expression. Funds are requested to transfer the assay to mammalian (preferably human) central nervous system cell lines and to validate the assay with a number of coded test compounds, both requirements for obtaining offered venture capital and subsequent creation of a viable startup company.