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Autism Speaks awards 16 new research grants funding more than $5 million over next 3 years

New York, N.Y. (April 8, 2010) 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."

Novel directions in early detection of autism

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)

From basic neuroscience to targeted treatments 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).

Innovative treatments for adults and nonverbal individuals with ASD

Two additional grants will each focus on novel treatments for understudied ASD populations. Because few interventions are designed with adults in mind, Evidence-Based Cognitive Rehabilitation to Improve Functional Outcomes for Young Adults with Autism Spectrum Disorders, (Nancy Minshew, M.D., University of Pittsburgh) and Social Processing, Language, and Executive Functioning in Twin Pairs: Electrophysiological and Behavioral Endophenotypes (Sara Webb, Ph.D., University of Washington) evaluate cognitive enhancement therapy aimed for use in training and coaching attention, memory, problem solving and social skills to improve adaptive behaviors in young adults with autism.

Finally, to aid non-verbal individuals, Laura DeThorne, Ph.D. and other investigators at University of Illinois will test a computer program that facilitates speech by providing visual feedback on production, loudness and pitch in Making Words Meet: Using Computerized Feedback to Facilitate Word Combinations in Children with ASD.

From laboratory studies to community effectiveness

Establishing the efficacy of treatment approaches does not always guarantee that a treatment will be adopted into practice. Barriers to implementation of evidence-based treatments are many. Therefore, the final step in the progression from basic research to improved health services must address how to enhance dissemination of best treatment practices to the autism community. To that end, three of the newly awarded treatment grants will focus on increasing access to interventions. Starting with an empirically validated early intervention known as Pivotal Response Training, one clinical trial will assess the effectiveness and efficiency of providing parent-training in a group rather than an individual format (Pivotal Response Group Treatment for Parents of Young Children with Autism, Antonio Hardan, M.D., Stanford University). A second clinical trial by Catherine Lord, Ph.D., University of Michigan Autism and Communication Disorders Center on Early Intervention in an Underserved Population addresses the question of access by underserved populations, including families of racial/ethnic minorities, lower education, or in rural geography, using a caregiver-implemented early intervention to examine the factors related to service utilization and satisfaction. Using a unique data resource, William McMahon, M.D., University of Utah will follow up a sample of over 200 adults with autism in 20-Year Outcome of Autism to understand their current symptoms, together with their needs, gaps and challenges in obtaining services. Finally, this project will also characterize the successes of adults with ASD.

"These types of studies are so important because unless we find a way to facilitate widespread, cost-effective means of bringing treatments and services to our families, we cannot successfully improve the lives of individuals with ASD, which is our mission. Without this last step, we will not have done our job," concluded Dr. Dawson.

See the complete list of funded basic and clinical studies and their abstracts and the treatment grants and the abstracts.

Another area of Autism Speaks research funding are studies leading to an understanding of how environmental factors influence risk for autism, and the interaction between genetic susceptibility and exposure to specific environmental factors. A major environmental initiative announced in the past year includes funding of the IBIS and EARLI studies which involve longitudinal studies of over 2,000 babies from early after conception through early childhood. These studies of babies who represent families with more than one individual diagnosed with autism seek to identify, in real time, environmental factors that may be associated with onset of ASD. Through its Environmental Factors Initiative, Autism Speaks is currently supporting a project led by Bruce Hammock, Ph.D. at UC Davis, to study Vitamin D insufficiency in children enrolled in the on-going Childhood Autism Risks from Genetics and the Environment (CHARGE) study. This study will provide a more complete picture of the source of Vitamin D insufficiency, the biological consequences, and the contributions to autism and co-morbid symptoms. The goal is to possibly identify a group of children with ASD who would benefit from Vitamin D supplementation therapy. Learn more about other environmental grants that have been funded.


Contact: Jane E. Rubinstein
Autism Speaks

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