SFARI

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.

Clinical Research Associates (CRA) is evaluating new potential treatments for autism, including R-baclofen.

Recent studies have provided compelling evidence that loss-of-function mutations in the CHD8 gene, which encodes an ATP-dependent chromatin-remodeling factor, are associated with an autism subtype characterized by macrocephaly, specific craniofacial features and gut immobility. The CHD8 protein modifies the structure of chromatin in the cell nucleus, and in vitro studies have suggested that CHD8 might function as a regulator of the developmentally important Wnt and PTEN signaling pathways. Tight control of both of these pathways is critical for normal brain development, and mutations that affect their activity have been strongly associated with autism and brain size. It is therefore important to test whether CHD8 functions as a regulator of these pathways during brain development.

Autism arises in early childhood, during a period of intense learning when many of the brain’s connections are modified by experience. Several autism-associated proteins also play important roles in memory formation.

The sense of touch allows us to navigate our physical world. The first step in tactile processing involves the activation of low-threshold mechanoreceptor neurons (LTMRs) with highly specialized endings in the skin. Social (affective) touch may be mediated by a unique class of slowly conducting C-fibers, the C-LTMRs.

There is growing support for the idea that both genetic and environmental risk factors contribute to autism. One environmental risk is maternal infection, as validated by large epidemiological studies showing links between infection during pregnancy and autism in the child. Similar associations were found with elevated immune responses in maternal serum or amniotic fluid. Also consistent with an immune pathophysiology are findings of activated microglia — immune cells within the brain — in people with autism, as well as dysregulation of immune-related genes in the brain, cerebral spinal fluid and periphery.

The etiology of autism is complex and mysterious. Autism has a strong genetic basis but there is remarkable diversity and heterogeneity in genes that are associated with the disorder. Despite this heterogeneity, a convergence of evidence suggests that disruptions in synapse function, neuronal activity and circuit formation are the origin of behaviors associated with autism.

Comprehensive studies of the human genome using high-speed DNA sequencing have identified new genes whose mutations appear to contribute to autism. One class of autism genes consists of regulators of the way that cells, including neurons in the brain, compact their DNA so that it can fit into the nucleus of the cell, while also being available for the selective production of proteins required for brain function. These genes, called chromatin regulators, appear to be among the most frequently mutated genes in individuals with autism. It seems that chromatin regulators control the production of proteins necessary for the development of neural circuits, and perhaps transmission of electrical impulses in the brain.

Duplication of a small segment of human chromosome 7 has been found in some children with autism. Lucy Osborne and her colleagues at the University of Toronto aim to understand the effects of duplication of this region, 7q11.23, on the growth and function of the brain. They plan to study this using a mouse model with a similar duplication.