World's largest autism science and advocacy organization awards 16 new research grants

Global autism science and advocacy organization advances research in basic science to translational research, from infancy to adults, from diagnosis to treatment, and from research laboratory to community

Autism Speaks, the world's largest autism science and advocacy organization, today announced the awarding of 16 new research grants totaling $5,223,743 over the next three years. The new grants will span basic research, which provides the innovative discoveries that form the building blocks of medical breakthroughs, to translational neuroscience research, which further develops these discoveries in animal models, to treatment research, which tests the efficacy of new interventions in clinical populations, to dissemination research, which explores methods for promoting the use of validated treatments in the community.

"The Autism Speaks research portfolio is one of the significant ways in which we support individuals impacted with autism spectrum disorders (ASD) and their families," said Mark Roithmayr, president of Autism Speaks. "The research is immeasurable in its contribution to early and confident diagnosis, and to identifying effective treatments and therapies that are at the core of improving the lives of individuals with ASD," he continued. "Without the incredible generosity of our community and corporate partners, and the funds raised at hundreds of Walk Now for Autism Speaks events throughout the year, this research would not be possible."

Autism Speaks Chief Science Officer Geraldine Dawson, Ph.D. remarked, "By funding both basic science and applied research, we are making investments in studies with promise for immediate impact as well as in studies that will move the field in new directions for the future."

Two studies to be funded are focused on developing new methods for very early detection of ASD. The first will validate a simple questionnaire that can be used by pediatricians to screen for ASD in one year-old babies (Using Parent Report to Identify Infants Who Are at Risk for Autism Spectrum Disorder (ASD) James Resnick, M.D., UNC at Chapel Hill). The second by Sabine Bahn, M.D., Ph.D., MRCPsych, Institute of Biotechnology, University of Cambridge will search for biomarkers for ASD by analyzing blood samples using a newly-developed technology platform called xMAP to identify a panel of proteins that can serve as diagnostic biomarkers for ASD (Biomarkers and Diagnostics for ASD)

The first step toward developing targeted biomedical interventions to address core symptoms of autism is to gain knowledge of the underlying biological processes that generate autistic behaviors. Several studies selected for funding provide this opportunity. For example, one of the most direct routes to uncovering the pathology associated with autism is to study brain tissue from individuals with ASD. Using post-mortem brain material, one of the studies will systematically investigate the affected brain networks, allowing identification of the cellular and molecular defects that characterize autism. Data from Neuropathology of the social-cognitive network in Autism: a comparison with other structural theories (Steven Chance, D.Phil, B.Sc., University of Oxford) will point the way toward biomedical treatments for autism.

Another approach to discovering the underlying biological mechanisms is to study the effects of autism risk genes on biochemical pathways, brain circuitry and behavior in animal models. For example, Functional study of synaptic scaffold protein SHANK3 and autism mouse model (Yong-Hui Jiang, M.D., Ph.D., Duke University) will examine the effects of mutations in the SHANK3 gene, which have been found in some individuals with autism. The gene creates a protein involved in synaptic function, disturbances of which are emerging as one of the central themes of autism pathophysiology. An additional mouse model study by Joshua Corbin, Ph.D., Children's Research Institute, Children's Hospital National Medical Center is looking at synaptic alterations in inhibitory transmission in the amygdala associated with Fragile X syndrome to evaluate the mechanism of altered inhibitory neurotransmission and potential correction of these defects (Elucidation and rescue of amygdala abnormalities in the Fmr1 mutant mouse model of Fragile X Syndrome).

While development of animal models is one of the key steps required for researchers to create and validate ideas for new treatment approaches, the field is also exploring biological measures that can empirically test the effects of a biomedical treatment on brain function. Association of Cholinergic System Dysfunction with Autistic Behavior in Fragile X Syndrome: Pharmacologic and Imaging Probes (Allan Reiss, M.D., Stanford University) will be the first to demonstrate the effects of a biomedical treatment (Donepezil) on brain function using functional magnetic resonance imaging (fMRI). This study will be conducted with individuals with Fragile X syndrome, approximately one third of who have a diagnosis of autism. If the study is successful, the technique can then be used in a wide range of treatment studies.

One of the most exciting findings in the past few years is the discovery that, in an animal model, it is possible to reverse some of the symptoms of ASD using biomedical interventions. Using information gained through studies of genetics and animal models, novel drug intervention strategies have been developed and are now ready to move into the human clinical trial phase (for more information about the path to drug discovery click here). Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation with IGF-1 (Omar Khwaja, M.D., Ph.D., Harvard Medical School/Children's Hospital Boston) will test whether the medication IGF1 can reverse the core ASD symptoms found in Rett syndrome. Randomized Phase 2 Trial of Rad001 (An Mtor Inhibitor) in Patients with Tuberous Sclerosis Complex (Mustafa Sahin, M.D., Ph.D., Harvard Medical School/Children's Hospital Boston), will evaluate the medication Rad001 to see if it can reverse the core ASD symptoms in Tuberous Sclerosis Complex. Both Rett syndrome and Tuberous Sclerosis Complex are developmental disorders closely related to ASD. In both of these instances, the biological pathways targeted by the drugs have also been implicated in ASD, suggesting that, if successful, these trials stand to serve as proof-of-principle to justify movement into clinical trials in other ASD populations.

"These studies are examples of how discoveries made at the molecular level can really be brought to bear on autism treatment," commented Dr. Dawson. "Our hope is that if these trials with syndromes that are closely related to ASD are successful, we can translate the knowledge gained to treatment studies of individuals with ASD. This is the first step toward developing medicines that target the core symptoms of ASD."

Another trial will focus on treating anxiety, which affects 1 in 4 affected individuals with ASD. Anxiety can be extremely debilitating for individuals with ASD, and can even hinder their responsiveness to behavioral interventions. Few medications have been tested to treat anxiety. One funded study will examine the ability of the medication Mirtazapine to treat anxiety symptoms in a randomized, placebo-controlled trial in children and adolescents with ASD (Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders, David Posey, M.D., Indiana University School of Medicine).

Another new study from Beth Israel Deaconess Medical Center/Harvard Medical School will focus on understanding sleep disturbances, a challenge that affects many people with autism and their families. This study by Robert Stickgold, M.D. will examine the nature of sleep disturbances in ASD, using state-of-the-art EEG techniques and also examining how such disturbances may affect memory consolidation and daily function (The effects of disturbed sleep on sleep-dependent memory consolidation and daily function in individuals with ASD).