PI3K/mTOR signaling as a novel biomarker and therapeutic target in autism
Suzanne and Bob Wright Trailblazer
Despite the high prevalence of autism in the USA, and the large impact autism spectrum disorders have on American families, society and economy, there are currently no drug treatments available that are directly targeted at the molecular mechanisms underlying autism. A major obstacle impeding the development of effective treatments is the high complexity of different factors that can contribute to autism such as gene mutations and environmental impact. These factors are affecting a variety of cellular and molecular functions, which complicates the identification of therapies that would be efficient in a large group of autistic patients. However, over the past years evidence has been emerging that a specific cellular signaling cascade, the PI3K/mTOR complex, is frequently disturbed in autism spectrum disorders via both inherited and exogenous mechanisms. The investigators propose that alterations within the PI3K/mTOR signaling cascade might be a common mechanism in many autism disorders, and therefore would potentially be a promising drug target. The overall goal of this research project is to develop assays that will identify molecular and cellular PI3K/mTOR dysfunctions as a common mechanism shared by autism spectrum orders of different etiologies. They expect that such assays, which analyze the function of proteins within the PI3K/mTOR complex, could be used to identify patients who would benefit most from a specific PI3K/mTORbased therapy, and might also be useful to screen for efficient drugs. This could help to prevent time-consuming and straining trial-and-error drug treatment in patients. To streamline the process and make it practical for diagnostic purposes, the research team will develop and optimize these assays for the use in lymphocytes isolated from fresh patient blood samples. The significance and novelty of this approach, as opposed to traditional methods that screen for gene mutations or chromosome abnormalities to identify common mechanisms in autism spectrum disorders, is the unique emphasis on the aberrant cellular signal cascades as a consequence of the disease-causing defects. This research approach has the potential to transform traditional strategies to identify disease-mitigating therapies in autism by shifting the focus from genes to cellular function.