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Small-molecule compounds for treating autism spectrum disorders

Ben Philpot, Ph.D.
University of North Carolina at Chapel Hill

Most cases of autism spectrum disorder are caused by defects in multiple genes, making the disorder particularly difficult to treat. In contrast, the loss of a single gene, UBE3A, causes a severe intellectual disability called Angelman syndrome, an autism spectrum disorder. Some forms of autism may also be caused by chromosomal duplications involving UBE3A.

Ben Philpot, Mark Zylka and Bryan Roth at the University of North Carolina at Chapel Hill have developed a high-throughput method of finding small-molecule compounds that alter the expression of UBE3A. The researchers plan to take advantage of fluorescent markers to track the expression of the gene in cultured neurons and in animals.

Bryan Roth has considerable drug discovery expertise and is the director of the Psychoactive Drug Screening Center at the National Institutes of Mental Health. Mark Zylka uses neurogenetic and molecular approaches to develop pain therapeutics. Ben Philpot is an electrophysiologist who has used mouse models of Angelman syndrome to pinpoint how single gene defects can impair the ability of the brain to encode new experiences.

Through their combined efforts, the researchers plan to identify small molecules capable of altering UBE3A gene expression and test the potential therapeutic value of these molecules in mice. Their approach, if successful, could be used to find small molecules capable of adjusting the expression of various autism-related genes, thereby paving the way for autism therapeutics.