Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with core behaviors that include social challenges and repetitive and restricted behaviors. Currently, there are no effective drug treatments for these core symptoms, and clinical progress is hampered both by an inability to compare results across clinical trials and the wide variability seen when trials rely on report-based outcome measures. There is, therefore, a pressing need to develop biomarkers that can serve as unbiased outcome measures and a need to optimize methodologies across trial sites.

Alterations in neuronal excitatory/inhibitory (E/I) balance have been implicated in a number of neurodevelopmental conditions, including ASD. Arbaclofen, a drug known to shift E/I balance through its actions as a GABA_B receptor agonist, has been the subject of phase 2 and 3 clinical trials in children and adolescents with ASD¹ and fragile X syndrome^2,3. Thus far, it remains unclear whether “failures” in these clinical trials simply reflect methodological issues associated with trial design, including large placebo effects and non-optimal outcome measures.

Emily Jones and colleagues argue that the relative low cost and non-invasive nature of electroencephalography (EEG), and its ability to assess alterations in E/I balance, make it an ideal technological platform for biomarker identification that could overcome current trial design limitations. In the current proposal, Jones and her team plan to incorporate EEG proxies of GABAergic functioning into two ongoing randomized clinical trials of arbaclofen in children and adolescents with ASD. These trials are being conducted in Europe (Principal Investigator: Celso Arango; ClinicalTrials.gov identifier: NCT03682978) and Canada (Principal Investigator: Evdokia Anagnostou; NCT03887676). Both the European and Canadian teams have been working closely together to make the trials as similar to each other as possible, and the intent is to ultimately pool the data from both trials into a single analysis (220 participants in total). Jones and colleagues plan to add an optimized EEG battery to all of the clinical sites involved in these trials (seven sites in total).

Incorporating EEG will add a relatively inexpensive and easily implemented measure into these ongoing trials and will ultimately help to advance the search for sensitive and predictive biomarkers of treatment efficacy that correlate with behavioral outcomes.

1. Veenstra-VanderWeele J. et al. Neuropsychopharmacology 42, 1390–1398 (2017) PubMed
2. Berry-Kravis E.M. et al. Transl. Med. 4, 152ra127 (2012) PubMed
3. Berry-Kravis E. et al. Neurodev. Disord. 9, 3 (2017) PubMed