Research published today in the scientific peer-reviewed journal Nature has discovered a potential treatment for Angelman syndrome, a neuro-genetic disorder similar to autism that occurs in one in 15,000 live births. By creating the motivational environment and access to resources that launched this research initiative in 2009, the Angelman Syndrome Foundation (ASF) is enthusiastic about the results of the work conducted by a team of scientists and doctors at the University of North Carolina (UNC) at Chapel Hill. The research, which is being continually funded by the ASF, has revealed that drugs currently used in the treatment of cancer may also be useful in treating Angelman syndrome.
“Three years ago I attended a scientific symposium hosted by the ASF, and after meeting with families of individuals with Angelman syndrome and networking among the Angelman syndrome community, I was inspired to conceptualize a research and drug discovery project that would identify how to restore proper function to the gene that causes Angelman syndrome,” said Ben Philpot, Ph.D., a scientist at UNC and one of the lead researchers behind this project. “The ASF provided the initial seed grant to launch this research project, and after countless hours of research and lab testing, our team has discovered a unique approach that may help treat individuals with Angelman syndrome and help them lead normal lives.”
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.
“This discovery is groundbreaking for the entire Angelman syndrome community, creating a sense of hope for individuals with Angelman syndrome, their families and caregivers that we have previously never experienced,” said Eileen Braun, executive director of the ASF. “This is exactly why the ASF was founded: to provide support for those affected by Angelman syndrome and to fund research that will lead to scientific breakthroughs such as today’s news. We are optimistic about the future and are looking forward to seeing what the next phase of this research uncovers.”
Through the research conducted, and for the first time in history, a drug compound has been used to restore proper function of the Ube3a gene. Since improper function, or “silence,” of the Ube3a gene is what has been determined to be the cause of Angelman syndrome, restoring proper function of the dormant Ube3a gene represents a possible therapeutic approach for treating the disorder. Using a unique process of screening more than 2,000 drug compounds through brain neurons – an extremely rare undertaking – 16 “unsilencing” compounds were discovered using a mouse model. The researchers then further experimented with those compounds with chemical derivatives of each compound to further enhance and target the intended affect of awakening the Ube3a gene.
“We have an exceptional team of 15 scientists, doctors and researchers at UNC who have spent the last three years focused on this project,” said Philpot. “Thanks to the intellectual ability, curiosity and experience of our team, and the in-house availability of technology and equipment at UNC that is usually only found at major pharmaceutical companies, we have made a significant advancement that will now lead us to the next phase.”
Conducting pre-clinical trials is the next step in evaluating how to make this treatment available to individuals with Angelman syndrome, which is essential to determining the right compound, the right dosage and the right delivery method prior to conducting clinical trials. Since the compounds that were found effective in activating the Ube3a gene are similar to drugs used to treat cancer and can be found in chemotherapy treatments, side effects may be similar to those experienced by individuals being treated for cancer, necessitating further research.
The ASF provided the initial grant in 2009 of $200,000 to launch this research and drug discovery endeavor. Organizations such as the Simons Foundation, the National Institutes of Health (NIH), and others then granted the UNC team additional funds for the project. In September 2011, the ASF granted another $400,000 to the research team for further drug discovery research and pre-clinical investigational work, creating a cumulative total of more than $3.6 million in grants to date. The research was conducted at UNC’s Carolina Institute for Developmental Disabilities in the Department of Cell and Molecular Physiology. Ben Philpot, Ph.D., Mark Zylka, Ph.D., and Bryan Roth, M.D., Ph.D. led the project with peer researchers Hsien-Sung Huang, John A. Allen, Angela M. Mabb, Ian F. King, Jayalakshmi Miriyala, Bonnie Taylor-Blake, Noah Sciaky, J. Walter Dutton Jr, Hyeong-Min Lee, Xin Chen, Jian Jin, and Arlene S. Bridges.