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Autism Spectrum Disorders

FREE

for Members

Autism Spectrum Disorders

Wednesday, December 1, 2010

The New York Academy of Sciences

Presented By

 

Autism Spectrum Disorders (ASD) affect an estimated one out of every 200 children who suffer from an array of deficits in social behavior, communication, attention and cognition. The degree of dysfunction and the specific deficits vary across individuals, making diagnosis difficult and complicating research into the underlying causes of ASD. Further, the optimal therapeutic strategy for an individual likely depends on the specific manifestation and etiology of their disorder. This meeting will feature researchers striving to advance our understanding of the causes of ASD and improve the ability for early diagnosis through genetic, neuroimaging, and behavioral techniques. The goal is to stimulate discussion on the discovery of potential biomarker and behavioral predictors of ASD to aid in early detection of the disorder and evaluation of the efficacy of therapeutic interventions.

This event will also be broadcast as a webinar.

Please note:
Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar. To access all speakers' presentations in full, we invite you to attend the live event in New York City where possible.

Networking reception to follow.

Agenda

*Presentation times are subject to change.


12:30 PM

Registration

1:00 PM

Opening Remarks
Sonya Dougal, PhD, The New York Academy of Sciences

1:15 PM

Genetic Signatures of Autism Spectrum Disorders
Matthew State, MD, PhD, Yale University School of Medicine

1:45 PM

Glimpses into the Autism Spectrum Disorders: A Genetic Perspective
Brett Abrahams, PhD, Albert Einstein College of Medicine

2:15 PM

Early Indicators and Predictors of Outcome in Infants and Toddlers with Autism Spectrum Disorders
Ami Klin, PhD, Yale University

2:45 PM

Coffee Break

3:15 PM

Electrophysiological Signatures of Language Impairment in Autism Spectrum Disorders
Tim Roberts, PhD, The Children's Hospital of Philadelphia

3:45 PM

Fragile X Syndrome: Clinical Trials and Biomarkers
Paul Wang, MD, Seaside Therapeutics

4:15 PM

Panel Discussion
Moderator: John Spiro, PhD, The Simons Foundation

5:00 PM

Networking Reception

Speakers

Organizers

John Spiro, PhD

The Simons Foundation

Dr. John Spiro is Senior Associate Director for Research at the Simons Foundation Autism Research Initiative (SFARI). The Simons Foundation is a private foundation based in New York City dedicated to advancing research in the basic sciences and mathematics. The mission of SFARI is to improve the diagnosis and treatment of autism spectrum disorders by driving, catalyzing and funding research of the greatest quality and relevance. Begun in 2006, the total size of the program has grown to approximately $60 million per year. John earned his undergraduate degree in Biology from Haverford College and his PhD from the University of California at San Diego. His thesis was based on work in the laboratory of the late Walter Heiligenberg and his postdoctoral work was with Richard Mooney at Duke University. His research interests were in cellular and systems neuroscience, and he focused on preparations where it was possible to forge links between cellular neurobiology and behavior. In 2000 John joined Nature Publishing Group as an editor at Nature Neuroscience, where he was involved in evaluating research findings across the field of neuroscience. In 2004 he moved to Nature as a Senior Editor on the biology team, where he oversaw a group of editors responsible for editorial decisions and peer review of manuscripts across all areas of neuroscience. In addition he gained experience in communicating science with both professional scientists and the public through his involvement in commissioning, editing and writing editorials, book reviews and other material for the journal and related web based resources. He moved to the Simons Foundation in 2007.

Sonya Dougal, PhD

The New York Academy of Sciences

Speakers

Brett Abrahams, PhD

Albert Einstein College of Medicine

Dr. Abrahams is interested in understanding relationships between disorders of human cognition and interplay between genes known to modulate risk. He received his Ph.D. in Neuroscience within the Center for Molecular Medicine and Therapeutics at the University of British Columbia in Vancouver, Canada. He later carried out postdoctoral training within the Neurogenetics program at the University of California, Los Angeles. Dr. Abrahams joined the Department of Genetics at Einstein this past summer and holds a cross appointment in Neuroscience. He has published widely in journals including Nature, NEJM, PLoS Genetics, and PNAS and currently serves on the Gene Advisory Board for the Simons Foundation Autism Research Initiative.

Ami Klin, PhD

Yale University

Ami Klin, Ph.D. is the Harris Professor of Child Psychology and Psychiatry at the Yale Child Study Center, Yale University School of Medicine. He obtained his Ph.D. from the University of London, and completed clinical and research post-doctoral fellowships at the Yale Child Study Center. He directs the Autism Program at Yale, which is one of the designated National Institutes of Health Autism Centers of Excellence. Dr. Klin's primary research activities focus on the social mind and the social brain, and on aspects of autism from infancy through adulthood. These studies include novel techniques such as the eye-tracking laboratories co-directed with Warren Jones, which allow researchers to see the world through the eyes of individuals with autism. These techniques are now being applied in the screening of babies at risk for autism in the Simons Laboratory of Social Neuroscience in Infancy. Beginning in 2011, Dr. Klin will lead an initiative to deploy cognitive science methods in high throughput screening for autism in infants in Atlanta. This initiative is a collaboration between the Marcus Autism Center, Children's Healthcare of Atlanta, and Emory University Department of Pediatrics.

Tim Roberts, PhD

The Children's Hospital of Philadelphia

Dr Roberts obtained his PhD from Cambridge University , England in 1992. He has subsequently been on the faculty at UCSF and the University of Toronto and is presently holder of the Oberkircher Family Chair in Pediatric Radiology and Vice-Chair for Research in the Department of Radiology at Children’s Hospital of Philadelphia as well as Professor of Radiology, University of Pennsylvania. His work in 4D functional imaging using biomagnetic recording as well as advanced MRI techniques (such as diffusion tensor imaging), specifically in the study of auditory processing and language has been supported by the National Alliance for Autism Research and is presently supported by Autism Speaks, the Nancy Lurie Marks Family Foundation, the Commonwealth of Pennsylvania and NIH. He has published in excess of 200 scientific papers, mostly in the field of physiologic and functional imaging, reviews grant proposals for NIH (standing member, DBD) and several equivalent international agencies (UK, Germany, Austria, Singapore, Israel, Cyprus, Canada, Holland), and serves on the executive committee of the American Society for Neuroradiology, the American Society for Functional Neuroradiology (President 2009-10) and the International Society for the Advancement of Clinical MEG (President 2009-11).

Matthew State, MD, PhD

Yale University School of Medicine

Matthew State, MD, PhD is the Donald J Cohen Associate Professor of Child Psychiatry, Psychiatry and Genetics at Yale University School of Medicine. He is the Vice Chairman for Research in the Department of Psychiatry and the Co-director of the Yale Program on Neurogenetics. Dr. State's laboratory studies the genetics of pediatric neuropsychiatric syndromes with a particular emphasis on autism spectrum disorders (ASD) and rare genetic variation. The lab uses molecular cytogenetics, linkage analyses, deep sequencing, copy number variation and whole exome sequencing in an effort to discover genes underlying these disorders. The lab has identified several strong candidates for involvement in ASD, including Contactin 4 (Fernandez et al., 2004 and 2008) and Contactin Associated Protein 2 (Bakkaloglu et al., 2008). Dr. State currently leads a collaborative genome-wide study of copy number variation in ASD funded by the Simons Foundation involving more than 5000 individuals. He has been supported by a ARRA "grand opportunity" grant and the Simons Foundation to conduct next generation sequencing in autism using both targeted and whole exome approaches and he has collaborated with his colleagues Murat Gunel and Richard Lifton at Yale to be among the first groups to demonstrate the power of this approach to identify novel genes involved in structural brain disorders (Bilguvar et al., 2010). Dr. State is a practicing Child Psychiatrist and the research efforts in his lab are focused on the translation of molecular genetic findings into new approaches to treatment across a variety of neurodevelopmental syndromes. 

Paul Wang, MD

Seaside Therapeutics

Paul Wang, M.D., is a developmental-behavioral pediatrician and Vice President for Clinical Development at Seaside Therapeutics, Inc.  Seaside Therapeutics is working to translate the basic science of learning and memory into targeted therapies for patients with Fragile X syndrome and for patients with autism spectrum disorders.  Dr. Wang is a graduate of Harvard College and Yale School of Medicine.  He also trained at the University of Michigan and the Salk Institute for Biological Sciences.  Prior to joining industry, Dr. Wang served on the faculty of Children's Hospital of Philadelphia, where he cared for patients with various neurodevelopmental disabilities, and where he studied the development of language and memory in children with genetic syndromes.  Dr. Wang remains actively engaged in the academic community, through leadership roles in the American Academy of Pediatrics (AAP) and the Society for Developmental-Behavioral Pediatrics, and in scholarly journal editorial roles.  He serves regularly on advisory panels for agencies such as the AAP, NIH, and CDC, on topics related to neurodevelopmental disorders and pediatric drug development.

 

Sponsors

For sponsorship opportunities please contact Cristine Barreto at cbarreto@nyas.org or 212.298.8652.

Presented by

Grant Support

This event is funded in part by the Life Technologies™ Foundation.

Promotional Partners

Asperger Syndrome and High Functioning Autism Association (AHA) Inc.

Abstracts

Genetic Signature of Autism Spectrum Disorders

Matthew State, MD, PhD, Yale University School of Medicine

The development of new genomic tools is dramatically increasing the pace of research into the genetics of autism spectrum disorders. Over the last several years the ability to look for rare genetic signatures of autism through analysis of copy number variation has been highly productive. The even more recent advent of high throughput sequencing and a precipitous decline in its cost t is further driving gene discovery. This presentation will review key findings with regard to sub-microscopic variations in chromosome structure in individuals with ASD and present new data regarding the genomic landscape of simplex autism - ie families with only a single affected individual. Recent examples of the application of next generation sequencing to gene identification in ASD and other developmental disorders will also be presented pointing to new and emerging opportunities to illuminate the molecular mechanisms of these disorders. 

Glimpses into the Autism Spectrum Disorders: A Genetic Perspective

Brett Abrahams, PhD, Albert Einstein College of Medicine

Twin studies suggest that heritability for the autism spectrum disorders is remarkably high. And yet despite important progress in the relationship between genetic variation and the ASDs an unexpected etiological heterogeneity is among the most reproducible finding to date. That at least a subset of genetic risk factors fails to respect clinical disease boundaries is additionally problematic but also informative with respect to disease architecture and future research. A variety of approaches aimed at tackling this heterogeneity, employing both rare and common approaches, will be discussed.

Early Indicators and Predictors of Outcome in Infants and Toddlers with Autism Spectrum Disorders

Ami Klin, PhD, Yale University 

With an estimated management cost of 35 to 80 billion dollars in the US alone, prevalence rates of close to 1:100, and a lifelong course, Autism Spectrum Disorders (ASD) present as an unfolding crisis for clinical, educational and community services. A disorder that creates itself over time, ASD can be attenuated and possibly prevented through early diagnosis and intensive early intervention. Focusing on cognitive science quantification of foundational social adaptive mechanisms, we developed eye-tracking based, low-cost behavioral assays that quantify the social disabilities in ASD. We then created "growth charts" of normative social engagement and used deviations thereof as early indicators of ASD. Our methods have yielded high sensitivity and specificity in early screening as early as 6 months of age, and predicted quantified outcome over a time span of greatest phenotypic variability. The Marcus Autism Center and Children's Healthcare of Atlanta will be deploying 10 screening sites in high-throughput pediatric care centers in Atlanta, providing full clinical and community supports including follow-up case management, clinical assessment and model early intervention. A potential partnership with the CDC will help quantify the impact of this program on the community. Our goal is not only to deploy translational science in the community; it is to develop a new model for health care delivery that will optimize outcome for children and their families.

Electrophysiological Signatures of Language Impairment in Autism Spectrum Disorders

Timothy P.L. Roberts, PhD, The Children's Hospital of Philadelphia

Language impairment is a core aspect of the autism phenotype, present in a significant fraction, but not all, children with diagnoses of autism spectrum disorders. Abnormal auditory processing has been suggested as a neural underpinning of such impairment. MEG determination of evoked response latencies to (i) simple isolated tones, and (ii) oddball (mismatch) paradigms of differing tones and/or vowels can be used to index successive stages of auditory processing. Separately, diffusion tensor magnetic resonance imaging (DTI) can be used to probe the integrity of white matter tracts of the auditory pathway (in particular the acoustic radiations).

Approximately 100 children (age 6-15years; ~40 typically developing; ~ 60 autism spectrum disorder) underwent successful MEG recording and DTI study. All data were recorded on a 275-channel biomagnetometer (VSM MedTech). MRI was conducted at 3T using a Siemens VerioTM system and a diffusion weighted imaging sequence with 30 non-collinear encoding directions and 2mm isotropic spatial resolution. Clinical determination of language impairment was assessed behaviorally using the Clinical Evaluation of Language Fundamentals-IV (CELF-4) test, using a threshold standardized score of <85 to indicate impairment.

Main findings of this study are: (1) delayed M100 response latencies (~10-20ms) in children with ASD compared to typically-developing peers; this delay does not distinguish children with autism spectrum disorders with and without concomitant language impairment (CELF-4 < or > 85). (2) Delayed "normalization" of M100 latency with developmental age in children with ASD compared to typically developing peers - M100 latency continues to shorten with age in both groups, but at a significantly slower rate in ASD. The age-mediated M100 latency in typical development is significantly associated with increasing fractional anisotropy (FA) of the acoustic radiations (interpreted as an index of white matter integrity/maturation). (3) MMF latencies are significantly prolonged in children with ASD, but this effect is especially pronounced in children with ASD with concomitant language impairment (~50ms). An age-covaried mixed-model with hemisphere (2), tone(2) and group(3) found a main effect of diagnostic group, with pair-wise comparisons all significant (p<0.05) indicating resolution of ASD with language impairment from ASD without language impairment and from typical development.

Electrophysiological measures of auditory processing at various stages may offer diagnostic insight with early responses discriminating ASD per se, and later responses showing resolution of language impairment sub-groups.

Fragile X Syndrome: Clinical Trials and Biomarkers

Paul Wang, MD, Seaside Therapeutics

Fragile X syndrome (FXS) is a single gene disorder that is almost universally associated with autistic symptoms, and which is the most common known genetic cause of Autistic Disorder, The "mGluR theory of Fragile X" has produced critical insights into the pathophysiology of FXS and, in turn, into potential "targeted therapeutics" for patients with FXS.  This presentation will review the neuroscience of FXS and will provide a summary of recently completed clinical trials in FXS, using mGluR  and GABA-ergic agents, the role of molecular and neurobehavioral biomarkers in these trials, and their potential relevance to autism generally.

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