FAST is thrilled to announce a grant to our continued partners and renowned scientists dedicated to advancing therapeutics for Angelman syndrome – David Segal, Ph.D., Jill Silverman, Ph.D., and the team at the University of California, Davis.  This grant provides the funding to build a lab devoted to Angelman syndrome (AS) research, establishing an infrastructure in which this team can evaluate multiple therapeutics simultaneously.

Dr. Jill Silverman is a behavioral neuroscientist with 18 years of training and experience focusing on preclinical rodent model systems with a strong emphasis in neurodevelopmental disorders and intellectual disability.

Dr. David Segal is a UC Davis professor of Biochemistry and Molecular Medicine with joint appointments in the Genome Center, the MIND Institute, and the Department of Pharmacology.  His area of expertise is in gene editing.

This funding will:

• Create a stable infrastructure for rapid testing of potential therapeutics in AS rodent models through at least 2025
• Train and retain staff dedicated to these studies, creating a new generation of scientists focused on AS research with combined expertise in molecular and behavioral components of AS
• Provide lab equipment and supplies
• Maintain AS cell lines and rodent model colonies at the University
• Provide long term stability for this dedicated team to keep their focus on identifying and evaluating potential therapeutics for the treatment of Angelman syndrome

Drug evaluation is incredibly complex as various animal models and cell lines need to be carefully and thoroughly evaluated in order to gain accurate conclusions. This team has dedicated their careers to perfecting this task, and have become key opinion leaders in understanding Angelman syndrome specific models. Dr. Silverman has developed the experimental design, in collaboration with Dr. Segal, validated and standardized testing procedures, and will oversee all aspects of results interpretation.  Dr. Segal will direct the molecular analysis of the experiments.  They bring with them an impressive team of geneticists and researchers with vast experience in working with disease specific models. This program will allow external researchers and industry partners to have access to this wealth of expertise.

There are multiple pharmaceutical companies that have potentially promising therapeutics for the treatment of AS.  However, they do not have expertise in AS, or the specific tools necessary to properly evaluate these drugs for this population.  This infrastructure grant allows AS experts to provide those services and elucidate if a potential therapeutic warrants further development toward potential human clinical trials.

As examples, two new projects are currently being sent to this UC Davis team:

• Evaluation of a small molecule in Angelman rodent models that was recently reported to rescue deficits in motor function and learning in an adult AS mouse model.  The lab will seek to independently validate these reports in mice and rats.

• Screening of a new drug library in AS reporter neurons.  These compounds will be evaluated in primary neuronal cultures and carefully evaluate for paternal Ube3a gene activation.

FAST is incredibly hopeful about therapeutics already in and nearing human clinical trials.  But we are not finished until every person with Angelman syndrome sees a meaningful therapeutic benefit.  We keep pushing, and this lab with these amazing individuals will be part of what enables us to do this even more efficiently and effectively.