Angelman syndrome occurs in one in 15,000 births. It is caused by the loss of expression of a protein made by the UBE3A gene in the brain cells. This gene plays a critical role in the function of the body’s nervous system. It leads to seizures, sleep disturbances, impaired communication development and motor and balance deficits.
Jill Silverman, associate professor in the Department of Psychiatry and Behavioral Sciences, and David Segal, professor of biochemistry and molecular medicine and faculty member in the UC Davis Genome Center, received the grant from the Foundation for Angelman Syndrome Therapeutics (FAST) to pursue treatments for the neurologic disease.
The researchers will use the grant funding to repurpose existing drugs and to screen for new ones. The grant will help create an infrastructure for testing potential therapeutics in rodent models of Angelman syndrome. In addition, it will fund the screening of compounds in brain cell neurons to determine what can turn the UBE3A on. The researchers will also explore non-UBE3A based therapies and look for ways to improve the symptoms of Angelman syndrome.
Collaborations to find cure to Angelman syndrome
The grant builds on the established collaboration between Segal’s Lab, with expertise in molecular analysis, and Silverman’s Lab, with expertise in behavioral research. This collaboration facilitates rapid testing of new compounds in cell, tissue and rodent models of Angelman syndrome. It also extends into training the next generation of researchers working on this rare disease.
“The close collaboration between our labs, the ongoing collaborations with other investigators at UC Davis and the support of the MIND’s Intellectual and Developmental Disabilities Research Center (IDDRC) provide the right combination to ensure that the experiments will be performed in a comprehensive and timely manner,” Silverman said.
The Silverman Lab tests the safety and efficacy of potential therapies on rodent models, and assesses improvements of symptoms such as cognitive abilities, gross and fine motor dysfunction, sleep disruption and seizures.
“While the technologies exist to test many therapeutics in cells and live animal models, the federal funding agencies are not always able to support such testing for the thousands of rare disorders,” Segal said. “That’s where patient advocacy groups such as FAST step in.”
Past FAST funding has enabled Segal’s Lab to create proteins that could turn on the affected gene in mouse models of Angelman syndrome. The Segal and Silverman labs have also worked with other FAST-funded researchers to create and characterize the first rat model of Angelman syndrome, which was reported January 2020 in Translational Psychiatry.
“FAST is enormously excited to fund the laboratories of Dr. Segal and Dr. Silverman to build a solid research infrastructure that can thoroughly evaluate multiple potential therapeutics for the treatment of Angelman syndrome,” said Paula Evans, chair and founder of FAST. “We are so appreciative of their personal and professional commitment to improving the lives of individuals with Angelman syndrome.”