SFARI

The goal of this project was to increase awareness of the need for brain tissue donation for autism research, and to thereby increase the number of people registered to donate and the number of actual donations. This project is the outreach program of Autism BrainNet.

The overarching goal of our work is to delineate the clinical and genetic heterogeneity within the Autism Spectrum Disorder diagnosis so that prognoses, treatments and preventive strategies can be implemented which are specific to each autism subgroup. We start by looking for biologically-based phenotypes which can be used to define discrete subgroups. One autism subgroup has been recognized based on findings generalized through often subtle differences in their physical features, indicating an insult to normal morphogenesis. Based on the premise that they would be genetically different from the rest, our goal has been to learn how to distinguish those children, characterize the ways they differ from children without dysmorphology and translate that information into best clinical practices.

Animal models play pivotal roles in understanding the relationship between behaviors and underlying brain circuits. One of the key features of autism is a deficit in social communication, including vocal communication. The primary animal models for autism research have been rodents because of the advantage of genetic manipulations. However, rodents lack certain social communication behaviors exhibited by primates, such as eye contact and high-level vocal communication. There is therefore a great need to develop new animal models, preferably nonhuman primate models, for autism research.

SPARK (Simons Foundation Powering Autism Research for Knowledge) is an autism research initiative that aims to recruit, engage and retain a community of 50,000 individuals with autism and their family members living in the U.S. Participation in this cohort will involve contribution of medical and behavioral information, mailing in saliva for genetic analysis, the potential option to have genetic findings related to autism returned, and consenting to be invited to participate in future research studies.

The mission of the Interactive Autism Network (IAN) is to accelerate autism spectrum disorder research in order to improve the lives of people living with this disorder. IAN has fulfilled an important need by offering valuable services (assistance with participant recruitment and data distribution) to the research community.

Two central challenges in autism research are defining specific neuronal abnormalities from genetic and environmental contributions and establishing preclinical models with human cells to test potential therapies. Autism is believed to be a disorder of neurodevelopment with a strong genetic liability. A large number of genetic risk loci have been identified by genetic association studies. Various animal models are being developed to explore the function of these genes in regulating neuronal development.

André Fenton and his group at New York University hypothesize that a common pathophysiology underlies the failures of cognitive flexibility that are characteristic of autism. Fenton aims to investigate the widely held ‘discoordination’ hypothesis that in individuals with autism, the neural computations within and between networks of cells that depend upon precisely coordinated neural activity are impaired.

Frick previously demonstrated a link between BKCa channel dysfunction, neocortical hyperexcitability and sensory hypersensitivity in the Fmr1-/y model of ASD. Drawing on this work, Frick will explore the potential of channel agonists for the therapeutic correction of phenotypes associated neocortical hyperexcitability/sensory hypersensitivity in genetic mouse models of ASD.