Therapeutics that Correct the Underlying Cause of Smith-Magenis Syndrome (SMS)

Project Abstract Smith-Magenis syndrome (SMS) is an autosomal dominant neurodevelopmental disorder characterized by the deletion of one Rai1 allele (Retinoic Acid Induced-1). As a transcription factor, this deletion causes a reduction in Rai1 expression and concomitant changes in expression of downstream targets, many critical to neurodevelopment and function. We have assembled a small library that were selected based on their ability to increase Rai1 expression. Our overarching goal is to demonstrate that Rai1 expression in SMS can be increased using a pharmacologic approach and many of the transcriptomic defects can be corrected.