About the Complexity of Autism: Findings from the Longitudinal European Autism Project (LEAP)

The EU-AIMS (European Autism Interventions - A Multicentre Study for Developing New Medications) is the largest single grant for autism in the world, and the largest for the study of any mental health disorder in Europe. EU-AIMS involves a novel collaboration between organisations representing affected individuals and their famillies (Autism Speaks), academia and Industry who for the first time in the world have come together to develop the infrastructure underpinning new treatments for autism. Patient organizations, academic and industry join forces to develop and assess novel treatment approaches for autism. The overall aim is to find new methods for the development of drugs for autism spectrum disorder (ASD).

ASD is a common neurodevelopmental disorder but effective medical treatments for the core symptoms are still lacking. Although novel genetic and pre-clinical approaches are beginning to identify aetiology-based treatment targets there are still considerable challenges in testing them in clinical trials. This includes the need for objective diagnostic, stratification, and outcome measures that are accepted by international regulatory authorities. The EU-AIMS Longitudinal European Autism Project (LEAP) is a multi-centre, multi-disciplinary study to identify biomarkers that will allow stratification of patients into more biologically homogenous subgroups; and that may serve as surrogate endpoints. We became the first joint academic-industry network to obtain scientific Qualification Advice from the European Medicines Agency (EMA). The EMA broadly endorsed the proposed population selection criteria and methodologies (cognitive, eye-tracking, EEG, MRI, and biochemical biomarkers) for patient stratification (Loth et al., 2015). Key recommendations included the need to establish sensitivity and specificity across all biomarker modalities, and to define cut-offs for quantitative stratification markers. As an exploratory study the large number of endpoints tested was recognized. Therefore, replication will be required, in particular to validate biomarkers as surrogate end points.

This presentation will provide the scientific background and rationale for the biomarkers that have been proposed and accepted, the design of the study (Loth et al. 2017; Charman et al. 2017), and first findings from the analyses of cognitive data, structure MRI, task-related MRI and resting-state MRI scans. These first findings support substantial biological heterogeneity, and indicate structural abnormalities in cortical thickness and surface area, altered connectivity between (but not within) neural systems, and cognitive deficits in spatial working memory and reversal learning, reading the mind in the eyes, and sensitivity to biological motion.

(EU-AIMS is supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115300 (EU-AIMS), resources of which are composed of financial contribution from the European Union`s Seventh Framework Programme (FP7/2007 - 2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies` in kind contribution).

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