ASO Treatment for a Better Understanding of AS Pathophysiology and Optimizing Therapeutic Efficacy

$199,100

Researchers will investigate in more detail the requirements of ASO-mediated rescue of behavioral phenotypes of an AS mouse model.

The most important questions they will attempt to address are:

1. How much ASO and how much UBE3A protein is really needed to get a rescue of behavioral phenotypes?
2. Is ASO treatment required throughout life?
3. When does ASO treatment have to start to get full rescue of epilepsy in AS mice?

Why This Study is Important

ASOs are exciting therapeutics because they replace the very gene product missing in individuals with AS. However, we don’t really understand how well they work when administered at different of development. We also don’t know how well they work in individuals with AS due to different causes (i.e. UPD or deletions). Even with two papers published in this area using UBE3A mutation mice, different ASOs may have different effects, and restoring UBE3A from both copies in mice with UPD and/or large deletion may have different results.

Study Update

(May 2023)  The first mouse cohorts have now been treated with different ASO doses and are currently being tested.