Autism is a common disorder with a prevalence of 1 in 88 worldwide (Centers for Disease Control 2008). Such diseases are mainly characterized by deficits in verbal communication, impaired social interaction, and limited and repetitive interests and behavior. Because autism is a complex spectrum of disorders, a different combination of genetic mutations is likely to play a role in each individual. 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. Moreover, mouse models do not represent the vast human genetic variation. 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. Thus far, the iPSC approach was used for syndromeic forms of ASD, such as Rett syndrome. Our preliminary data shows that one can actually model for idiopathic autism and provide evidence for an unexplored developmental window in ASD wherein potential therapies could be successfully employed. The current proposal uses human somatic cells converted into iPSC-derived neurons. We anticipate gaining insights into the causal molecular mechanisms of ASD and to discover potential biomarkers and specific therapeutic targets for ASD.
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 study neurons and other cell types 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, we plan to use this resource for a drug-screening platform, aiming to rescue defect in ASD-derived cells. The development of this type of pharmacological therapeutic approach in California will serve as an important proof of principle and stimulate the formation of businesses that seek to develop these types of therapies in California with consequent economic benefit.