A precision medicine approach to investigate autism-related functions of altered blood proteins as potential targets for autism therapy

Autism spectrum disorder is a neurodevelopmental condition that has no cure and no single known cause, which is likely due to the broad variation in clinical symptoms and severity levels. These facts highlight a significant need for precision medicine in tackling the causes of autism and developing tailored therapies for selected groups of patients who share similar clinical features. Therefore, we have recruited a well-defined cohort of autism and control subjects and we have stratified them based on their blood proteomic profiles. Remarkably, we have identified several upregulated blood proteins in autism, which are also associated with the clinical severity of autism symptoms. Interestingly, our identified blood proteins in autism are related to neuronal functions, which include synapse assembly, cell adhesion, and neurodevelopment, which suggest a functional relevance of these blood proteins in the pathophysiology of autism. Here, we will determine the functional impact of altered blood proteins in the pathophysiology of autism through scRNA-Seq of iPSC-derived cortical neurons generated from subjects exhibiting upregulated blood proteins. Also, we will use a gain of function approach in Drosophila to validate the role of these proteins in inducing autism-relevant behaviors. We expect these results to determine autism-related functions of altered blood proteins for a defined group of autism patients as an important approach towards precision medicine.

Hamad Bin Khalifa University (HBKU)