FAST grants New Investigator Award to Drs. Michael Sidorov and Abigail Dickinson
Research Update: FAST grants New Investigator Award to Drs. Michael Sidorov and Abigail Dickinson

FAST is excited to announce a newly awarded grant on an exciting project that is being headed by Dr. Michael Sidorov, from Children’s Research Institute at the Children’s National Hospital, and Dr. Abigail Dickinson from UCLA at the Center for Autism Research and Treatment. This New Investigator Award will support the evaluation of peak alpha frequency as a potential Electroencephalogram (EEG) biomarker for individuals living with Angelman syndrome, for potential use in clinical trials. With the rapid increase in pre-clinical and clinical work investigating multiple therapeutic approaches that could potentially transform the clinical picture of Angelman syndrome, there has been a large unmet demand for reliable, robust, and measurable biomarkers that relay clinically relevant improvements after a treatment. In funding this work, FAST is further supporting biomarker research that is integral to the success of ongoing and future clinical trials.

EEG is a reliable, safe, translational, and quantifiable test that is utilized in Angelman syndrome regularly to assess for seizure activity. This test can also measure brain waves that are different from neurotypically developing individuals, and measure how they can change over time, back to a more typical level. This is called “spectral power”. This power has been found to be incredibly useful for Angelman syndrome and has been tagged as one of the leading biomarkers by the Angelman syndrome Biomarker and Outcome Measure Consortium (ABOM), which is a collaborative pre-competitive group of individuals that have come together quarterly from pharmaceutical companies, academia, and the foundations (FAST, FAST-Australia, and ASF).

An EEG is an objective biomarker in Angelman syndrome as it allows for the measurement of the underlying electrophysiology of brain wave activity, which has been correlated with overall function on standardized tests, like the Bayley Scale of Infant and Toddler Development (BSID) and the Vineland Adaptive Behavior Scale (VABS). Research previously performed by Dr. Sidorov and his team has established elevated low frequency (~2-4 Hz) delta rhythms as a promising biomarker for AS, however the amplitude of delta differences is broadly affected by age wherein older individuals have more moderated delta dynamics. To widen the search for a potential EEG biomarker in adult individuals living with Angelman syndrome, this work will quantify peak alpha frequency (PAF), or the frequency at which oscillations are strongest in the alpha band of the EEG. This will focus on adolescents and adults individuals with AS using previously collected EEG data from the robust Natural History Study that has been collecting data since 2006. Peak alpha frequency is a well-established measure of neural network development and cognitive function that is typically impaired in individuals with neurodevelopmental disorders. This work will characterize PAF in AS and correlate this with clinical severity outcomes across a broad range of ages (1->25 years) laying the groundwork for discovery of an exciting, new electrophysiological AS biomarker that expands upon the elevated delta power biomarker and may be more applicable for the population of older individuals.

“FAST is incredibly excited to support this work as there is a great need to understand how these electrophysiologic changes on EEG are manifesting in all ages, not just the younger individuals where most of the data has been collected,” said Dr. Allyson Berent, Chief science officer, FAST. “This could potentially be a leading biomarker in clinical trials for AS, and if the standard delta power is not as profound in adolescent and adult individuals, as it is in the younger population, it is very important that we discover other measures that will capture similar change for more advanced ages.”

“Receiving a new investigator grant from FAST allows my lab to develop Angelman EEG biomarkers for clinical trials. Developing new biomarkers is so important in order to give current and future trials the best possible chance of succeeding. It was a hard few years starting my new lab during the pandemic, and this FAST award makes such a difference in jumpstarting our work. I am also thrilled that this FAST award brings Dr. Abigail Dickinson and her immense EEG expertise into the AS community.” -Dr. Sidorov

“My early research career has studied brain-behavior relationships in Autism, focusing on EEG markers that can guide targeted interventions and promote optimal development. I am especially keen to develop accessible EEG methods suitable for populations who have been underrepresented in neuroscience research, including individuals with cognitive and language difficulties. So far, I have used this approach to study brain mechanisms and development in infants, children, and adults with Autism. However, connecting with Dr. Sidorov highlighted new opportunities to extend these EEG biomarkers to Angelman syndrome. It’s an exciting time for clinical trials in AS, and I feel very fortunate to work with Dr. Sidorov on novel biomarkers that could help target and track intervention in individuals with AS. I’m still very early career, and this opportunity would not be possible without a new investigator award from FAST. Most importantly, this FAST award will allow Dr. Sidorov and I to pool our experience, methods, and ideas to drive progress biomarkers that can benefit the AS community as quickly as possible.” – Dr Dickinson