Cure Autism Now Announces Unprecedented 25 Research Grants for 2005

October 10, 2007

As we end another year, Cure Autism Now is so grateful for the support and generosity that touch us each day. Through donations from individuals, foundations and corporate sponsors, who believe in our ability to accelerate science to find a cure for autism, we have been able to fund an unprecedented 25 research grants for next year.

We are humbled by the people who volunteer, organize and participate in our fundraising events, including our extremely successful WALK NOW program. And we are inspired by the families who courageously fight for a better life for their loved ones with autism and still find time to support Cure Autism Now in a variety of ways. Because of you, we are more hopeful than ever that autism will soon succumb to science so we can prevent, treat and cure this debilitating disorder.

Cure Autism Now achieved a number of milestones in 2004. We raised more money than ever, we secured important new funding for autism research and awareness from the federal government, and we funded more exciting new research projects than at anytime in our nine year history. Autism is in the news almost weekly and Cure Autism Now is often cited as a leading force within the community. With the rising prevalence of autism in the U.S. (1 in every 166 children), autism now affects everyone--it's a national concern.

With this in mind, we are pleased to announce that Cure Autism Now will fund a record 25 new research projects in 2005. During the 2004 grant review cycle, we experienced the highest level of grant applications in our history--over 200 inquiries and nearly 150 qualified grant proposals. Importantly, the quality of research has improved greatly and now spans a diversity of topics, including molecular biology, genetics, environmental co-factors and the neuro-cognitive aspects of autism. More than ever, we are encouraged by the progress we are making in understanding what might cause autism and how it might soon be treated.
We are able to fund this unprecedented number of grants and expanded research due to the tireless fundraising efforts and incredible generosity of all of you that have joined us in our mission. It's my pleasure to give you a preview of the exciting research that will begin next year. Please read on to see a list and description of the 25 research projects that your commitment to people affected by autism has made possible. Thank you again for your support and we look forward to a prosperous year in 2005.

Warm holiday wishes,

Peter Bell
Chief Executive Officer

Cure Autism Now 2005 Research Grants

GENETICS: Searching DNA for mutations

The Prevalence of Mutations in X-Chromosome Linked Genes (Pilot Project Award)
Jozef Gecz, Ph.D., Women's and Children's Hospital, Australia
Genes and the environment perform a delicate balancing act in the determination of the outcomes of many disorders, including autism. Research in other diseases has shown well-documented examples of patients and families where a defect in a given gene can be identified as the primary cause. Autism is a complex genetic disorder, with many genes contributing. This study will look at genes on the human X-chromosome, which has been linked to various developmental issues (including autism). Dr. Gecz will be using samples from Cure Autism Now's AGRE gene bank to study two genes (ARX and STK9) his lab had previously tied to another disorder, X-linked mental retardation . Because many patients with X-linked mental retardation also have autism, Dr. Gecz will now be screening autism patients for mutations in the ARX and STK9 genes.

DLX Genes and Autism (Pilot Project Award)
John Rubenstein, M.D., Ph.D., University of California, San Francisco
Although it is known that genetics contribute to the susceptibility to develop autism, the identity of the genes that contribute to the disorder are poorly understood. A recent model of autism, co-proposed by Dr. Rubenstein, postulates that some forms of autism are caused by an excess of excitation-to-inhibition in neural circuits controlling cognitive and emotional development. This suggests that an analysis of genes that promote inhibition in the neural circuits should be conducted in people with autism. This study will analyze the DNA sequences of a series of genes (called the DLX genes) that control the development and function of forebrain inhibitory neurons. Dr. Rubenstein's preliminary evidence shows that ~5% of autistic people in the Autism Genetic Resource Exchange data set have mutations in these genes, suggesting that further analysis is warranted.

Search for an Autism Gene on the Y Chromosome (Young Investigator Award)
Marwan Shinawi, M.D., Baylor College of Medicine
This study will attempt to identify the biological and molecular basis of autism. Specifically, the intent is to try to discover the cause of autism and develop a laboratory test that would be used to diagnose patients with autism. The study will also attempt to explain the higher male predisposition to autism. The fact that the methods used till now have failed to provide strong evidence for a major causative gene for autism suggests that many genes might contribute to autism or other genetic mechanisms may be involved. Dr. Shinawi will test whether changes that do not involve nucleotide sequence such as changes in chromatin structure and nucleotide sequence methylation can alter gene expression and eventually cause autism. The heritable changes in gene function that occur without a change in the DNA sequence are called epigenetic changes. The DNA methylation is a chemical modification of the nucleotide sequence itself that can change the expression of different genes. The emphasis will be on genes that are located on the Y chromosome, an area that has been under investigated. If an epigenetic basis is identified for autism, there might be the potential for therapeutic intervention using compounds such as folic acid, which are known to alter the regulation of genes that are subject to regulation by DNA methylation.

IMMUNE SYSTEM: Looking for evidence of dysfunction in autism

Immune Genes and Abnormal Brain Development in Autism (Pilot Project Award)
Lisa Boulanger, Ph.D., University of California, San Diego
In this study Dr. Boulanger outlines the connections between autism and immunological challenges. She will study how a variety of maternal infections, such as influenza, may affect the development and behavior of the fetus, even when the fetus shows no signs of direct infection itself. The fetal impact appears to be the result of a relatively nonspecific aspect of the maternal immune response, but is reflected in altered cytokines in the fetal brain. This study will use mouse models and autistic children to explore whether the expression of immune genes is altered in the autistic brain, perhaps highlighting the potential for immune-based diagnostics, treatment and prevention.

Sex Differences in Autism: The Potential Role of Oxytocin Signaling (Pilot Project Award)
Kathryn Anne Ellerbeck, M.D., M.P.H., University of Kansas Medical Center
The effects of oxytocin on immune function may be as important as its role in social affiliation, for which it originally received attention in autism research. Oxytocin functions in conjunction with G-proteins as a signaling neuropeptide, with effects on immune function. This study will investigate whether young children with autism have aberrant oxytocin levels in blood, if their G-proteins are abnormal, and if gender differences in oxytocin expression result in varying levels of immune response. The investigators suspect that increased Oxytocin action in the limbic system may "protect" girls from autism. The study will also explore whether abnormal oxytocin levels are associated with immune activation and altered cytokines, shedding light on possible immunological mechanisms that may relate to social function and autism.

ENVIRONMENT: The impact of our surroundings upon developing autism

Do Environmental Factors Play a Role in Autism? A Test Using Natural Experiments (Pilot Project Award)
Dennis K. Kinney, Ph.D., McLean Hospital/Harvard Medical School
Whether environmental factors play an important role in causing autism is a crucial - and hotly debated - question. Many studies report unusually high rates of medical problems during the gestations and births of persons who later developed autism, suggesting that environmental factors occurring before or around the time of birth may contribute to the development of the disorder. Skeptics, however, argue that the same genes that cause autism also cause these high rates of pregnancy and birth complications. The most powerful scientific approach to deciding this issue -- an experiment in which pregnant women were randomly assigned to low vs. high stress conditions - would clearly be unethical. We use an alternative strategy that uses natural disasters as "experiments of nature" to test the hypothesis that exposure to stressful events during vulnerable weeks of gestation significantly increases risk of developing autism. Anonymous data on more than 4,000 persons with autism from three different states, as well as on 2 million general population births in these same states, will be studied to investigate whether autism rates are significantly increased among individuals who were in certain weeks of gestation at the time their mothers were exposed to natural disasters such as extremely destructive earthquakes, hurricanes, and severe blizzards. Confirmation that pre- and perinatal environmental stressors play a significant role in causing autism would have important implications for the treatment and prevention of autism.

INFORMATION PROCESSING/COGNITIVE ABILITY: Determining how the autistic brain functions

Processing of Emotional Facial Expressions in Autism: The Role of the Amygdala (Pilot Project Award)
Ralph Adolphs, Ph.D., California Institute of Technology
We know that people with autism have difficulty in social functions, but we know little about the causes of this difficulty. Dr. Adolphs will study how the brains of people with autism process social information and try to associate this processing to a particular brain region called the amygdala, which has been linked to autism. The research is aimed to gain insight into how the brains of people with autism process faces. Subjects in the study will be asked to look at pictures of faces and to make judgments about the emotional state of the face, while their eye movements are being measured. Dr. Adolphs has previously shown that people who have damage to the amygdala also have difficulty in this task, but can get better at discriminating facial expressions after receiving instruction. Ultimately the researchers hope that this study will lead to earlier diagnosis, better prediction of social dysfunction and improved strategies for rehabilitation of patients with autism.

Functional magnetic resonance imaging of cerebellar learning in autism (Pilot Project Award)
Greg Allen, Ph.D., University of Texas Southwestern Medical Center
The cerebellum is the most consistent site of brain abnormality in autism. For instance, over 95% of autistic cases examined at autopsy show some form of cerebellar pathology, the most common being a reduced number of Purkinje neurons, a key component of neural circuitry in the cerebellum. Functional MRI (FMRI) investigations by Dr. Allen have found that individuals with autism display an abnormally widespread pattern of cerebellar activation during simple motor tasks. This functional deficit could be due to the described loss of Purkinje neurons. The proposed investigation will use FMRI, a non-invasive approach to examining brain function, to study cerebellar function in 18 adult individuals with autism and 18 normal controls as they perform the serial reaction time task (SRTT). The SRTT, a standard tool for studying the neural basis of learning, is known to involve the cerebellum, and individuals with autism show impaired learning on this task. Thus, the proposed study will help determine the relationship between such impairment and cerebellar dysfunction, and more importantly, it will investigate a potential neurofunctional link between cerebellar pathology and the symptoms of autism.

The Role of Perceptual and Attentional Disturbances in the Early Diagnosis of Autism (Pilot Project Award)
Michelle O'Riordan, Ph.D., City University, London
Research has recently shown an unusual ability in people with autism to notice minor features or changes in the environment. Recent studies have been used to find experimental examples of this superior ability to detect hidden pictures and sounds in both children and adults with autism. The results of these studies suggest that enhanced target detection is a feature of the disorder which remains stable throughout development from at least 7 to 40 years of age. This study will assess the possibility that this ability is present in very young infants with autism. Therefore, this study will explore the use of visual and auditory search tasks as additional tools for the early diagnosis of autism. The first benefit of this study is that visual and auditory search tasks should provide more objective experimental measures than observation methods. A second advantage is that such methods can be used prior to the development of social skills and require minimal social interaction. A third reason that visual and auditory search tasks might provide an additional tool for early diagnosis is that they are aimed at assessing phenomena which have been associated selectively with the autistic disorder.

Neurophysiological Investigations of Social Attention in an Animal Model (Pilot Project Award)
Michael L. Platt, Ph.D., Duke University Medical Center
Humans are fundamentally social. During even the simplest of interactions, social cues and expectations guide where we look and pay attention, and these orienting movements in turn often betray our own deepest intentions and desires. The inability to attend to social signals or to use social cues to jointly orient attention with others profoundly diminishes the ability of people with autism and related disorders to function normally in human society. Understanding the brain mechanisms supporting social attention is thus a fundamental problem for contemporary neuroscience. Unfortunately, the mechanisms responsible for guiding attention in social situations remain poorly understood. This study will determine how a crucial structure known as the parietal cortex uses social information to guide attention. We will begin by developing a new behavioral model of human social attention in monkeys. Our preliminary data show that monkeys, just like normal humans, attend to social cues, such as faces and where they are looking, and thus serve as a superb animal model of human social attention. We will then use this new animal model to probe how neurons in the parietal cortex respond during social attention. The preliminary data indicate that social cues activate attention-related neurons in the parietal cortex, suggesting that normal social attention probably depends on meaningful social signals reaching this area of the brain. These observations suggest the possibility that social attention deficits in autism may be improved by enhancing the transmission of social signals to the parietal cortex. The development of new treatments for autism and related disorders thus may benefit directly from improved understanding of social attention mechanisms in an animal model.

Crossmodal Interactions in Autism (Pilot Project Award)
Ladan Shams, Ph.D., University of California, Los Angeles
Individuals with autism suffer from social and communication deficits. In addition, many of them perform differently from non-autistic individuals in a broad range of cognitive and perceptual tasks. In an attempt to find a common underlying cause for these perceptual differences the investigators suggest that interaction between distinct brain regions is impaired in autism, even at very initial stages of perceptual processing. Key deficits at these early stages of processing can have ramifications for higher-order perceptual, cognitive, and social processes. Previous studies have shown that individuals with autism have difficulties in performing tasks that demand using information from different senses. Our investigation will focus on the integration of simple visual and auditory stimuli. We will compare the degree of a known sound-induced visual illusion and the brain activity (ERP) elicited by the illusion between adults with autism and control groups. Dr. Shams predicts that individuals with autism will show a weaker illusion and smaller increase in sound-induced visual activity. Contingent upon verification of the researcher's predictions, they will study the role of training with synchronized auditory and visual stimuli in improving multi-sensory integration mechanisms in autism. The preliminary findings with non-autistic individuals have revealed that such training does indeed lead to enhancement of auditory-visual integration processes. A similar effect should be seen in individuals with autism.

Face Processing in Autism: An Investigation at Multiple Levels (Young Investigator Award)
Kate Humphreys, Ph.D., Carnegie Mellon University & CPEA
Many people with autism experience difficulties when recognizing and perceiving faces. They also have difficulties in other areas of visual processing; in particular they tend to focus on the parts of objects or patterns, possibly at the expense of the overall whole. Dr. Humphreys thinks that the problems people with autism have with faces may be one of the end results of their more fundamental perceptual style of concentrating on details rather than seeing things as wholes. The investigators believe it is crucial to determine where the fundamental deficit lies, as this is likely to have strong implications for remediation strategies: if the primary deficit is at the level of face processing, then remediation should target face processing per se; if, however, the primary deficit is more fundamental, then remediation strate
ies should focus on earlier visual processing. This study will use a cognitive neuroscience approach that includes both the psychological (what is happening in autism at the level of behavior) and neural (level of brain activation) components by conducting behavioral tests and neuroimaging tests with adults with autism, focusing on both face processing and lower level perceptual processing. We will then look for links between performances on face processing and perceptual processing in each individual, with a view to uncovering where the primary difficulty lies.

Neural Bases of Visuospatical Processing in High-Functioning Autism (Young Investigator Award)
Rajesh Kumar Kana, Ph.D., Carnegie Mellon University
Research studies have revealed structural and functional abnormalities in the brain in autism. While these studies are consistent with the prediction that autism is primarily a disorder of brain functioning, no single neuropathological feature as yet has been identified unambiguously and no single model of pathophysiology is currently accepted. Several research studies have indicated that many individuals with high functioning autism have superior or intact ability in certain domains of functioning. For example, many individuals with autism are good visual thinkers. This study will investigate such advantages that high functioning individuals with autism have by using magnetic resonance imaging technology to study the integration of various brain regions when individuals with autism perform problems involving visuospatial thinking. Using these images, it is possible to detect which areas in the brain are active during processing of a particular problem. These results will be compared with typical control participants' brain scans while performing the same problems. This research is important as it will provide information about the nature of visual and spatial processing in autism, and may indicate specific type of processing differences. A clearer understanding of the way that individuals with autism process information will lead to the development of enhanced interventions.

Functional Magnetic Resonance Imaging of Social Perception in Adults with and without Autism Spectrum Disorders (Young Investigator Award)
James P. Morris, Ph.D., Duke University
This study will use functional magnetic brain imaging (fMRI) techniques to study the neural basis of social perception deficits in high functioning adults with autism. fMRI is a non-invasive imaging method that can localize changes in blood oxygenation levels in the brain - an indirect measure of underlying neural activity. Throughout the past decade fMRI has been used to examine brain activation in humans related to countless sensory and cognitive processes. The tool has also been used, with great success, to characterize the neural basis of many different clinical disorders. Social perception refers to the initial stages of evaluating the intentions of others by analysis of eye gaze direction, facial expressions and body movements. Recent advances in virtual reality technology and stimulus presentation capabilities have allowed researchers to study how humans process social information. Despite these advances, little is known about the neural basis of social perception deficits that are often associated with autism. This study will combine fMRI and virtual reality technology to help identify the neural basis for social perception deficits in autism.

Implicit Learning and Autism Spectrum Disorders (Young Investigator Award)
Christopher J. Smith, Ph.D., Mount Sinai School of Medicine
Long before the emergence of a conscious effort to learn, infants and young children are acquiring information from their environment. This information aids in the typical development of social and communication skills. Individuals with autism experience strong deficits in these areas and it is quite possible that these deficits are related to and impaired ability to acquire information from their surroundings without conscious effort. This ability is referred to as implicit learning and has been tested in a number of different populations where explicit learning ability is affected or grossly impaired. The results from these studies strongly suggest the resiliency of implicit processes when compared to explicit functioning. This study is designed to test if individuals with autism display an impaired mechanism for implicitly learning information in a social context. Two different tasks have been designed. One of the tasks will determine if a sequence can be implicitly learned through the use of very neutral images, and the other task will determine if the sequence can be learned through the use of faces with different emotional expressions (a social task). If learning is impaired on both tasks, the results may suggest general neurological impairments. If learning is impaired on the social task only, it may imply the need for a new therapeutic direction to increase the processing time of social information.

CELLULAR AND MOLECULAR DEFICITS: Pinpointing the underlying defect(s) in autism

Biochemical and Cellular Characterization of Neuroligin-3 Mutation Associated with Autism Spectrum Disorders (Pilot Project Award)
Davide Comoletti, Ph.D., University of California, San Diego
Today, autism spectrum disorders are accepted as being complex inheritable biological disorders that interfere with the normal development of the brain. A major limitation in the study of autism has been the difficulty in identifying the altered genes. Recently, two studies reported that mutations of two genes on the X chromosome, neuroligin-3 and neuroligin-4, have been linked to autism-spectrum disorders and mental retardation. Other genetic analyses found correlations between autism and the genes for neuroligin-1 and neuroligin-2. The neuroligin genes encode for a family of proteins expressed in the brain that govern development and maintenance of synapses, the structures which allow nerve cells to communicate with each other. Dr. Comoletti has established that the mutation found in neuroligin-3 prevents the correct cellular localization of the protein and thus impairs its normal function. This project will study the function, degradation, and localization of the normal and mutated neuroligin proteins in nerve cells in order to determine their exact function in the brain. Therapeutically, mutated neuroligin proteins could be affected by intervention with directed antioxidants and reducing agents.

Functional Studies on the New Candidate Gene for Autism (Pilot Project Award)
Jean G. Steyaert, M.D., Ph.D., Katholieke University Leuven, Belgium
A novel approach to finding candidate genes for autism has allowed this research team to identify several candidate genes for autism. The approach consists of searching for "broken" genes in rare subjects with autism and specific chromosomal anomalies where only one gene is damaged. Three of these genes, neurobeachin, amysin and CLIC4, participate in the same biological pathway(s) in brain cells: regulated secretion. This pathway plays a role in regulating how nerve cells grow and differentiate, and probably also in controlled cell pruning (apoptosis) which is a normal part of early brain development. Deregulation of nerve cell growth and pruning has been demonstrated in the brains of persons with autism. The aim of this study is to investigate Dr. Steyaert's belief that errors in the genes neurobeachin, amysin and CLIC4 lead to problems with regulated secretion, thus effecting development of brain cells and perhaps resulting in autism. Dr. Steyaert will examine where the genes are expressed in the developing brain, and what happens if their function is disrupted in a mouse model. Such understanding may eventually lead to more focused biological treatments for autism.

DIAGNOSIS/ASSESSMENT: Markers and tests to measure autism

Use of Functional Behavioral Assessments to Evaluate Stereotypy and Repetitive Behaviors in a Double-Blind, Placebo Controlled Trial of Citalopram (Pilot Project Award)
Latha Soorya, Ph.D., Mount Sinai School of Medicine
Individuals with autism spectrum disorders show marked variability in their response to interventions. The purpose of this study is to evaluate the use of functional behavioral assessments (FBA) as tools to elucidate the effects of treating autistic children with the serotonin reuptake inhibitor (SSRI), citalpram. SSRIs are a class of medications used to target stereotyped and repetitive behaviors in autism. FBAs are methods developed from the field of applied behavior analysis used to observe how a behavior changes in relation to the events that precede (i.e. antecedents) and follow its occurrence (i.e. consequences). FBAs have been valuable tools in behavioral and medication studies. In medication studies, they are used to increase our understanding of why some individuals respond to medication and why others do not show improvements. This study will focus on the use of descriptive FBAs to identify which children respond and do not respond to medication, to evaluate patterns in repetitive and stereotyped behaviors, and to evaluate the relationship between FBAs and other outcome measures used in clinical trials. The addition of FBA methods to evaluate outcome in medication studies is an important step for research methodology in treatment of individuals with autism spectrum disorders.