Periodic Reporting for period 3 - THERAUTISM (New molecular targets and proof-of-concept therapies for Autism Spectrum Disorders)
Reporting period: 2023-03-01 to 2024-08-31
Autism is a complex multifactorial disorder affecting the development of the brain. Nowadays it accounts for more than 1 in 100 child births worldwide. Autism spectrum disorder is diagnosed based on behavioural criteria: deficit of social communication and interaction and restrained or stereotyped behaviours. There is no medicine that help to improve social symptoms and autism management. The EU-funded THERAUTISM project aims to shrink this autism research gap from the identification of new targets to the first therapeutical development of some of these targets. The first goal is to identify and validate all the substrates in a small and very conserved brain circuit that underly social interaction and if they are dysregulated in autism. The project will also investigate the possibility for two substrates of social behaviours – after it takes into account the properties of a new protein function – to restore these new targets and rescue social deficits in different preclinical models of autism. Overall, the THERAUTISM project aims to identify new therapeutic targets and innovative therapies for autism spectrum disorders. The project is divided in two parts: 1) identification of the new molecular targets, and 2) the study of two identified substrates of social behaviours and the most effective therapeutical approach to restore their function.
Since the beginning of the project in March 2020, we successfully identify the most suitable preclinical models of autism and have implemented all the technics and set up experimental conditions in the lab. Regarding the identification of the new molecular targets, we already have half of the samples and expect to identify the first targets within a year. For the investigation of the two identified substrates of social behaviours, we are currently preparing two research articles on their involvement in social interaction and their dysregulation in autism. We formally identified that both are differentially dysregulated in preclinical models of autism, and especially in response to social interaction. We have started to develop and test the best strategical option to improve social interaction.
Two research gaps remain in autism, the identification of new therapeutical targets and the development of potential treatment to improve the core social symptoms. The THERAUTISM project will provide significant results to the autism field, through the identification of the molecular substrates underlying social interaction and of the best therapeutical option that could be applied to the two identified substrates.