Project: Altered Translation in Autism

Acronym	ALTRUISM (Reference Number: NEURON-047)
Project Topic	Autism spectrum disorder (ASD) is a complex lifelong neurodevelopmental condition of high prevalence with atypical social, behavioral and cognitive function, which creates a high economic burden for public health. The extraordinary complexity and heterogeneity of genotypes and phenotypes are major challenges when investigating ASD. In spite of elusive etiology, dysregulated protein synthesis has emerged as a point of convergence among mechanisms underlying ASD. This project aims to understand the pathophysiology of ASD downstream of mutations in FMR1, PTEN, TSC1/2 and RPL10, which directly impinge on protein synthesis. Molecular understanding of ASD will enable efficient patient stratification and identification of predictive biomarkers for a possible drug repurposing of already existing therapies targeting translational regulators. This will be achieved by using a combination of modern high-throughput technologies (-omics) for quantification of transcriptomes and proteomes along with morphological and functional studies in iPSC derived neurons and brain organoids harboring distinct mutations. As proof-of-principle, we will screen blood samples from deeply phenotyped patients for newly identified biomarkers. The personalized medicine approach proposed here will pave the way for new ASD treatments, significantly ameliorating life quality of patients and their families, and benefitting dramatically on the health systems worldwide.
Network	NEURON Cofund
Call	Multinational Research Projects on Transnational Biomarkers in Brain Disorders

Project partner

Number	Name	Role	Country
1	Istituto Europeo di Oncologia	Coordinator	Italy
2	Institut Pasteur	Partner	France
3	Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft	Partner	Germany
4	ETH Zurich - Swiss Federal Institute of Technology, Institute for Neuroscience	Partner	Switzerland
5	CIUSSS du Centre-Ouest-de-l’Île-de-Montréal – Hôpital général juif - Lady Davis Institut	Partner	Canada