Methods of modulating atxn2 expression

Abstract

The expression of the ATXN2 gene can be modulated to reduce the amount of ataxin-2 protein produced by a cell. This can be accomplished by administering to the cell an effective amount of an ATXN2 modulating agent. Screening was performed with 428,749 compounds for lowering expression of an ATXN2-luciferase reporter in HEK-293 cells, with a multiplexed cell viability assay to ensure target reduction in the absence of cytotoxicity. Secondary qHTS assays included a CMV-luciferase reporter expressed in HEK-293 cells as well as a biochemical assay using recombinant luciferase to detect inhibitors of the reporter enzyme. A diverse set of compounds were found to reduce ATXN2 expression, including compounds targeting HSP90, cardiac glycosides, NaK-ATPases and topoisomerases.

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