New publication evaluates EEG as a biomarker for Angelman syndrome
This week we are highlighting a new publication from Dr. Anne Anderson’s lab at Baylor College of Medicine that evaluates EEG as a tool, or biomarker, to objectively measure therapeutic efficacy in Angelman syndrome. This work falls within FAST’s Pillar 4 — Accelerating and Preparing for Clinical Trials in our Roadmap to a Cure 2.0.
This work is particularly exciting for our community right now, given the multiple ongoing and emerging clinical trials. This study illustrates that certain aspects of an EEG can be quantified, and they may be found to change in response to a therapeutic intervention. This can potentially be used in trials as a biomarker to measure changes in AS after treatment. This is something that the Angelman Syndrome Biomarker and Outcome Measure Consortium (ABOM) has been working very hard to identify because biomarkers (like EEG) can often be more objective to measure than clinical outcomes that focus on how a person feels or functions (for example measuring communication ability). Biomarkers often include lab tests, imaging (X-ray, MRI, etc), or other measurable and objective assessments, like measuring blood pressure to assess if a medication is helping to lower blood pressure.
Potential EEG biomarkers (e.g. elevated delta power) and seizure-related EEG read-outs (e.g. spike activity or notched delta), have been well documented in individuals living with AS, however there is still uncertainty around what they mean and whether therapeutic intervention can alter these measures in a meaningful way. In the work published here, Dr. Anderson and her team sought to retrospectively evaluate EEG data in individuals with AS after administration of minocycline, a commonly used antibiotic that has been suggested to reduce seizure susceptibility. The EEG measures were evaluated to see if there was an ability to document change pre and post treatment. A trial evaluating minocycline in Angelman syndrome was conducted in 2012 (NCT01531582).
EEG was collected at baseline (prior to the intervention), 8-weeks after minocycline treatment, and 8-weeks after a washout period (where the drug completely left the body). At each timepoint they evaluated delta power, total power, and spiking activity in the EEG to see if there was any evidence of change. At baseline, typical EEG characteristics were seen that are consistent with the Angelman syndrome diagnosis including elevated delta and total power, as well as increased spiking activity. Following an 8-week minocycline treatment cycle, there were no significant differences observed in the power or the spiking. However, at the 8-week washout period both delta power and total power were significantly reduced, as was the spiking activity in certain brain regions.
While this work is promising for our community in support of EEG as a tool to measure brain activity changes in response to therapeutic intervention, especially given the multiple ongoing and emerging clinical trials, it is limited by what those brain activity changes mean. The next steps will be to correlate EEG with behavior such as motor function, sleep, seizures, cognition or communication to see if changes in EEG can predict functional outcomes.