Autism Spectrum Disorders (ASD) are common and severe neurodevelopmental disorders characterised by deficits in social communication and repetitive and restricted behaviours (including sensory anomalies). It is estimated that approximately 1% of children and adults are affected by ASD world-wide; that is nearly 5.5 million patients in the European Union (EU).
Currently, no effective medical treatments for the core symptoms are available and prior drug trials have been largely unsuccessful. Over the past years, major progress in the understanding of the genetics of autism, the development of in vitro and genetic animal models, and identification of several neurobiological phenotypes have opened new avenues for the identification of aetiology-based treatment targets. However, these advances were accompanied by increasing recognition of a further hurdle; namely the profound phenotypic and genetic heterogeneity between patients. For example, approximately 70% of people with ASD have one or more comorbidities. Likewise, hundreds of risk genes have been identified, yet each explains only a small percentage of patients. Last but not least there is poor understanding and knowledge on how the condition and the needs of the patients change in the different stages of life (e.g. in children, versus adolescents, versus adults with ASD). This highlights the need to move beyond one-size-fits-all treatment approaches and to develop stratified approaches that are tailored to the specific needs and biological profiles of particular patient subgroups.
This project offers a unique opportunity to create a European-wide research strategy in collaboration and in alignment with US-based efforts that overcome key bottlenecks in the development and testing of treatments for ASD. It will build the necessary capacity, within Europe, for the conduct of future trials, while also contributing towards a more unified approach to research in ASD within Europe in the clinical sciences.
Specifically, to meet these objectives, the project will:
Validate stratification biomarkers to enable identification of more homogeneous clinical and / or biological subgroups for clinical trials, including for co-morbidities, in particular epilepsy, but excluding psychosis/schizophrenia;
Create a European-wide clinical trials network trained to GCP standards to facilitate large-scale clinical trials;
A fully aligned and integrated global framework for clinical trials in ASD and co-morbidities
Enhance drug discovery efforts by testing translatability of drug effects (new and/or repurposed) between patients with ASD with and without co-morbidities and preclinical models to enable and feed a sustainable pipeline of innovative treatments.
This project will have a major impact on this field and in parallel contribute towards the Innovative Medicines Initiative 2 (IMI2) goals as outlined in Article 2 of the IMI2 Council regulation:
Identify patient sub-populations for particular treatments through validation and qualification of stratification biomarkers.
Development of a Europe-wide infrastructure to accelerate and tailor patient recruitment to targeted (adaptive) clinical trials.
Based on these deliverables, the project will set new standards for industry and allow potential identification of personalised medicines for patients in highly characterized patient groups.
Development of a unified approach to clinical research in ASD within Europe.
A better understanding of common vs. distinct pathophysiological mechanisms underlying ASD subgroups, i.e. genetic, neurobiological and/or accounting for clinical variables such as comorbidities, developmental stage and sex.
The integration in the IMI action of complementary activities conducted in parallel in Europe and the US will result in a significantly larger patient population studied, in the combination of clinical trial results, and parallel validation and regulatory submissions of R&D tools. All this will not only increase the probability of success, but will also contribute to significantly accelerating R&D in a very complex research field.