Fluorescent RNA foci assay for FXTAS drug discovery

PROJECT SUMMARY Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder that that predominately affects adults over the age of 50. Individuals afflicted with FXTAS develop tremor, ataxia, Parkinson-like symptoms, and slowly lose their cognitive abilities to the point that they are completely dependent on others for care. Currently, there is no cure. Therefore, there is a strong need to discover first-in-class drug treatments capable of preventing and/or reversing FXTAS disease progression. FXTAS is a trinucleotide repeat disorder caused by premutations in the fragile X mental retardation 1 (FMR1) gene. RNA gain-of-function toxicity from the expanded trinucleotide tracts in FMR1 is thought to be the primary cause of FXTAS pathology. In the nucleus, expanded trinucleotide tracts form RNA aggregates that sequester RNA-binding proteins and splicing factors from normal cellular functions and trigger cell degeneration. Therefore, the discovery of small molecules that disru