Benjamin Philpot

Ben Philpot, UNC-Chapel Hill

“It is important to identify and validate biomarkers for upcoming clinical trials, and also to develop best practices for clinical management of anxiety, sleep disturbances, GI issues, and other issues, each of which could be its own individual goal. Furthermore, we need to identify pathway specificity and mechanistic basis for seizures to lead to better anti-epileptics. In addition, I think we need to:

  • Understand the mechanism of imprinting to suggest molecular targets for Ube3a unsilencing
  • Reboot drug discovery for Ube3aq unsilencing agents, as very few compounds have been screened to date
  • Develop novel approaches to identify relevant Ube3a substrates
  • Elucidate isoform-specific roles of Ube3a”
Ronald Thibert

Dr. Ron Thibert, Massachusetts General Hospital

“I would love to see more studies looking at the role of GABA – I am convinced it plays a big role in seizures in both populations, ASD in Dup15q, and sleep and anxiety in both. Clinically, we have seen some amazing responses to CBD – not just seizures but also non-epileptic myoclonus and in some cases sleep and anxiety. Since its availability is limited in most states a trial would be awesome – I think it could be huge in AS. We have seen some benefit in Dup15q as well but not like we have in AS.”

Wen Hann Tan

Dr. Wen-Hann Tan, Boston Children’s Hospital

We need to determine the minimum amount of UBE3A expression that is required to have at least some verbal language. We are in the process of writing-up our findings from our Natural History Study which assessed verbal skills. Dr. Stormy Chamberlain and I have discussed doing some functional studies in iPS-derived neurons to try to determine the “why” in folks who have more verbal ability. I think this may be useful and important data because if re-activation of the silenced paternal UBE3A is one therapeutic strategy for AS, then we need to know the extent to which the UBE3A gene needs to be re-activated to detect clinical improvement.”