Preclinical Autism Consortium for Therapeutics

The overarching aim of our consortium is to target the unmet need for medical treatments for the core diagnostic symptoms of autism spectrum disorder (ASD). We will provide early preclinical evaluation of proposed compounds to discover beneficial actions in multiple animal models. Our strategy is designed to de-risk the path to clinical trials, and lower the barrier for pharmaceutical and biotechnology companies to pursue autism therapeutics.

Three specific aims are designed to accomplish this purpose:

  1. Identification of robust, well-replicated phenotypes relevant to autism in genetic animal models. Standardized behavioral and physiological assays for the diagnostic and associated symptoms of ASD are in place in the laboratories of the principal co-investigators. Rodent genetic models will be chosen to satisfy three criteria: (a) the gene mutation has been reported in multiple cases of autism and accounts for a sizable population of ASD patients; (b) the mutation has been generated in both mice and rats, in lines that are accessible to the consortium laboratories; (c) published findings indicate deficits in social behaviors and other traits relevant to ASD. 
  2. Evaluation of tool compounds acting through mechanisms relevant to the genetic mutations. For each robust, replicated autism-relevant phenotype identified in each mouse and rat genetic model, the pharmacological agent will be tested for its ability to restore normal behaviors and physiology. Results will be assembled into a comprehensive database, to create a results matrix of compound x assay x model. Positive and negative findings of therapeutic potential will be published in scientific journals. Findings in the database will be available online to academic investigators, pharmaceutical researchers, and other stakeholders.
  3. Dissemination of best practices for animal model assays relevant to autism. High quality, standardized behavioral and physiological assays in mice and rats, employed by the consortium, will be taught to young investigators and PIs seeking to upgrade their testing methods, through annual training courses in the laboratories of the Principal Co-Investigators.