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Angelman Syndrome Infrastructure Grant Update

From Dr. David Segal, Dr. Jill Silverman, and Dr. Kyle Fink at UC Davis

Having rebounded from the limiting conditions of COVID-19 restrictions, the Infrastructure Team is hard at work for the Angelman syndrome (AS) community. We have been busy building a lab that is devoted to Angelman syndrome research, establishing an infrastructure in which our group can evaluate multiple therapeutics simultaneously. The four key areas that we have been working on are:

Area 1) Antisense Oligonucleotides (ASO): Our top priority is testing rat specific ASOs in our AS rat model to understand the molecular biology that underlies effects observed in clinical trials. This information could help inform near term clinical trials as well as test our translation research endpoints.

Area 2) Known Compounds: A major area of focus is evaluating drugs that have shown some utility for Angelman syndrome in the scientific literature. We are currently performing behavioral pharmacology on three novel compounds in the AS mouse.  We know that these compounds are safe and effective in other conditions, and if they are validated and well characterized, showing robust behavioral changes in AS models, they could be prioritized for clinical trials.

Area 3) Unknown Compounds: We are working with various pharmaceutical companies to robustly screen and evaluate their proprietary compound libraries/therapeutic targets. Our aim is to de-risk new potential therapeutics for efficacy in Angelman syndrome. We are screening 2-3 libraries of compounds in fluorescent reporter neurons. In this way, we capture compounds previously identified for particular targets (Area 2) as well as completely new compounds that we don’t yet know to be useful.

 Area 4) Biomarkers: We are starting new experiments to look for biomarkers that might provide molecular clues to response to treatments. We have prioritized 24 candidate proteins to be assessed in multiple brain regions, cerebral spinal fluid (CSF), and plasma in multiple rodent models of AS that are currently being maintained at UC Davis through the infrastructure effort. These candidates will also be assessed in individuals with AS, in collaboration with Dr. Jessica Duis, using plasma and the existing biobank of samples in her lab. This effort leverages our unique tools and animal models with the knowledge and assistance of the broader scientific AS community.

We will continue to provide updates on a regular basis! 

"As you can see, we are hard at work trying to understand how these drugs can affect the course of Angelman syndrome. We are grateful to FAST for giving us the opportunity to bring the impressive capabilities at UC Davis to serve our Angelman community"

Dr. Segal.