Autism and autism spectrum disorders (ASD) are complex neurodevelopmental diseases that affect 1 in 88 children in the United States. Such diseases are mainly characterized by deficits in verbal communication, impaired social interaction, and limited and repetitive interests and behavior. One of the major impediments to ASD research is the lack of relevant human disease models. ASD animal models are limited and cannot reproduce the important language and social behavior impairment of ASD patients. Reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells, iPSCs) has been accomplished using human cells. Isogenic pluripotent cells are attractive from the prospective to understanding complex diseases, such as ASD. Development and maintenance of neuronal circuits requires a complex series of events involving coordinated communication between multiple cell types over multiple length scales of space and time. The possibility that exosomes, a type of extracellular membrane vesicles, function as a novel type of cell-cell communication to establish and maintain neuronal circuits have not been explored. We propose to test the hypothesis that exosome-mediated signaling is deficient in ASD. We have established a human ASD prototype model, with clear and robust differences. We anticipate gaining insights into the causal molecular mechanisms of ASD and to discover potential biomarkers and novel specific therapeutic targets.
Statement of Benefit to California:
Autism spectrum disorders, including Rett syndrome, Angelman syndrome, Timothy syndrome, Fragile X syndrome, Tuberous sclerosis, Asperger syndrome or childhood disintegrative disorder, affect many Californian children. In the absence of a functionally effective cure or early diagnostic tool, the cost of caring for patients with such pediatric diseases is high, in addition to a major personal and family impact since childhood. The strikingly high prevalence of ASD, dramatically increasing over the past years, has led to the emotional view that ASD can be traced to a single source, such as vaccine, preservatives or other environmental factors. Such perspective has a negative impact on science and society in general. Our major goal is to a novel hypothesis based on our preliminary data, suggesting that a new type of cell-cell communication may impact neurons derived from induced pluripotent stem cells generated from patients with ASD. If successful, our model will bring novel insights on the identification of potential diagnostics for early detection of ASD risk, or ability to predict severity of particular symptoms. In addition, the development of this type of diagnostic approach in California will serve as an important proof of principle and stimulate the formation of businesses that seek to develop early ASD detection tools in California with consequent economic benefit, and maintaining California's position as a leader in stem cell research.