Small molecule un-silencer of UBE3A for Angelman syndrome

A blood brain barrier-permeable small molecule that allows functional paternal UBE3A alleles to be expressed could help treat Angelman syndrome, which is caused by mutations in the maternal UBE3A gene, by decreasing expression of the antisense long non-coding RNA (lncRNA) UBE3A-ATS, which silences the gene in neurons.

In primary mouse neurons, a high throughput fluorescence-based screen of a chemogenetic library from Pfizer Inc. (NYSE:PFE), identified a small molecule CDK2/CDK5 inhibitor and its analogues that increased paternal expression of UBE3A, in a CDK2 and CDK5-independent manner. ...