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Research published on June 6th in the scientific peer-reviewed journal Neuron has discovered the possible underlying cause of seizures in individuals with Angelman syndrome, a neuro-genetic disorder similar to autism that occurs in one in 15,000 live births. Seizures are a potentially life-threatening symptom that 90 percent of those with Angelman syndrome experience.  Funded by the Angelman Syndrome Foundation (ASF), the research was conducted by a team of scientists at the University of North Carolina (UNC) at Chapel Hill. The team’s leader, Ben Philpot, Ph.D., professor of cell and molecular physiology at UNC, was also the research lead on the discovery announced in December 2011 about a potential treatment for Angelman syndrome using drugs currently used in the treatment of cancer. 

“Our goal with this research was to identify brain defects that might contribute to cognitive impairments or seizures that people with Angelman syndrome experience. The ultimate goal of this research is to help identify treatments to improve cognition and prevent seizures from occurring, as seizures experienced by individuals with Angelman syndrome are very difficult to treat,” said Philpot. “Individuals with Angelman syndrome already experience atypical neuronal developmental; however, this study specifically revealed how a dramatic imbalance between neuronal excitation and inhibition may contribute to cognitive impairments and seizures in Angelman syndrome.”

Angelman syndrome is a congenital disorder causing severe neurological impairment that appears in newborns and lasts for a lifetime. During fetal development, the loss of function of a particular gene in the brain occurs, resulting in neurons functioning incorrectly and causing deficits in development. Individuals with Angelman syndrome experience development delay, lack of speech, seizures, and walking and balance disorders, and typically exhibit a happy demeanor characterized by frequent smiling, laughter and excitability. 

Using electrophysiological methods to record neuronal activity in mice with Angelman syndrome, the team at UNC found defects in the neurotransmitter signals sent from inhibitory neurons to decrease activity in excitatory neurons. A balance between inhibitory and excitatory neurons is essential for proper neuron function, yet individuals with Angelman syndrome experience an imbalanced decrease in both neurons’ activities. However, this research discovered a disproportionately large decrease in inhibition compared to a smaller decrease in excitation, creating a hyper-excitable state that is believed to contribute to seizures in many individuals in Angelman syndrome. This fluctuating, improperly regulated brain activity might also underlie cognitive impairments in Angelman syndrome. 

“For families of individuals with Angelman syndrome, this is incredible news because seizures are a major concern, as sadly they have claimed the lives of many loved ones with Angelman syndrome,” said Eileen Braun, executive director of the ASF. “The Foundation was founded to provide families with direct support and aid important research endeavors, and today’s announcement is a direct reflection and accomplishment of our mission. The Foundation is committed to helping ensure that this research—as well as other important research initiatives—continues so that ultimately quality of life is improved for individuals with Angelman syndrome.”

Organizations such as the National Institute of Neurological Disorders and Stroke, the Simons Foundation, the National Eye Institute, and the National Institute of Mental Health granted the UNC team additional funds for the project. The research was conducted at UNC’s Carolina Institute for Developmental Disabilities in the Department of Cell and Molecular Physiology by Michael L. Wallace, Alain C. Burette, Richard J. Weinberg and Benjamin D. Philpot, Ph.D. 

ABOUT THE ANGELMAN SYNDROME FOUNDATION
The Angelman Syndrome Foundation's mission is to advance the awareness and treatment of Angelman syndrome through education and information, research, and support for individuals with Angelman syndrome, their families and other concerned parties. The ASF sponsors Angelman syndrome research through grants to researchers pursuing promising avenues of discovery. Since 1996, the ASF has funded 66 research grants totaling more than $4.6 million. The ASF has awarded a majority of these funds ($4.3 million) beginning in 2005.