By funding this groundbreaking work from Ben Philpot and his team, the Angelman Syndrome Foundation is investing in one of the most direct paths toward a true treatment for Angelman syndrome. This research tackles the core biology of Angelman syndrome by focusing on how to turn on the intact but silenced paternal UBE3A gene, which represents one of our most promising therapeutic strategies.
Because individuals with Angelman syndrome lack the maternal copy of UBE3A, reactivating the paternal gene could restore the function that is missing in the brain. Until now, scientists have not been able to study paternal UBE3A silencing at the depth and scale needed to pinpoint what controls it. Dr. Philpot’s team has changed that by building a powerful reporter mouse model and the capability to grow hundreds of millions of neurons, making it possible to run the first genome-wide CRISPR screen to identify the genes responsible for keeping paternal UBE3A turned off.
By uncovering these targets and testing whether they can be safely modulated with drugs, this work provides a clear roadmap for designing therapies that directly unsilence the paternal gene. For the Angelman community, this means deeper biological understanding, precise therapeutic targets, and meaningful progress toward treatments that address the condition at its source.