Beth Israel Deaconess Medical Center, Boston, MA
Principal Investigator: Richard L. Sidman, M.D.
Stem Cell Injections Prevent Loss of Cerebellar Purkinje Neurons
The most consistent pathological abnormality found in autopsied cases of individuals with Autism Spectrum Disorder (ASD) is a decrease in number of cerebellar Purkinje neurons. Purkinje neurons are at risk in many neurological disorders, and undergo cell death in circumstances that may cause debilitating damage in other brain areas. The investigators’ belief that stem cells may help ASD patients comes from their experiments on mice with different neurogenetic disorders which cause selective destruction of Purkinje neurons. They injected neural stem cells (NSCs) into mouse cerebellum and found that mice injected with NSCs as babies, before Purkinje neurons were destined to die, grew up healthy, with cerebella that contained abundant Purkinje neurons. They established that stem cells had rescued the mouse’s Purkinje cells from dying! Before testing stem cell therapy in humans with brain disorders, the investigators must learn in mouse experiments what types of stem cells to use, how many cells to inject, how often, and by what routes, to maximize their distribution though affected brain regions with minimal discomfort. They have discovered that tissue plasminogen activator (tPA) is increased 10-fold in the cerebellum of one of their mouse mutants, and that tPA reverts to normal in mice they treated with NSCs. They plan to test the idea that tPA may act as a common “death mechanism” in many diseases affecting Purkinje neurons, and that therapy with stem cells should be directed at correcting the chemistry involved in this mechanism. The use of stem cells for rescue of Purkinje neurons would be of benefit regarding restoration of cerebellar function and may provide clues to chemical abnormalities that would lead to therapeutic recovery in brain regions that are more subtly affected in ASD, though with serious behavioral consequences.
Department of Neurology - Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center, Boston, MA
Principal Investigator: Christopher Walsh, M.D., Ph.D.
Recessive Genes for Autism and Mental Retardation (Co-funded with The Simons Foundation)
Twin studies suggest that autism has a large genetic component; however, few potential autism susceptibility genes have been identified. The goal of this project is to use special genetic populations to map and identify autism spectrum disorders (ASD) genes to better understand their classification, pathogenesis, and potential treatments. Preliminary data show that the large families and patterns of consanguinity that characterize special populations such as the Arabic countries of the Middle East facilitate the recognition of recessively inherited neurological disorders. The investigator will identify appropriate pedigrees that show children with autism, and in which parents are related to one another, suggesting that recessively acting genes may be causing ASD in those families. He will then take advantage of this consanguinity to map and hopefully clone these recessive ASD genes. The investigator will focus on Arabic populations of the Middle East since these populations also show “founder mutations” which are restricted to certain groups, and which further facilitate precise gene mapping. This study may provide new insights into patterns of inheritance and genetic causes of autism spectrum disorders.
Christopher A. Walsh Laboratory
Broad Institute, Massachusetts Institute of Technology, Cambridge , MA
Principal Investigators: David H. Skuse, M.D., Ph.D., Eric Lander, Ph.D, Pamela Sklar, M.D., Ph.D.
Confirmatory study of influence of EFHC2 genetic variant on complex phenotype in x-monosomic females
This research aims to identify genetic influences in the development and function of neural systems that may be disrupted in individuals with impaired social and cognitive functions by studying individuals with Turners syndrome, a condition in which one of the two X chromosomes normally found in females is missing or incomplete. Because individuals with Turner syndrome have similar social cognitive deficits as many individuals with autism, and because autism is a condition in which males outnumber females significantly, the results of this research may shed light on genetic vulnerability to autism. The goal is to map a genetic locus to the X-chromosome associated with emotion-processing deficits in individuals with Turner syndrome. Researchers intend to investigate through a replication study, the hypothesis that the EFHC2 gene contributes to social cognitive difficulties in Turner syndrome, and the hypothesis that specific allelic variants in the gene contribute to vulnerability to autism.
Broad Institute, Massachusetts Institute of Technology
Children's Hospital of Philadelphia, Philadelphia, PA
Community Responses to Autism: Public Health and Public Policy Challenges
The NLM Family Foundation provided support for a conference on policy issues in the delivery of care and services to individuals with autism entitled, "Community Responses to Autism: Public Health and Public Policy Challenges". This event was held at the Children's Hospital of Philadelphia in June of 2005. Topics of discussion included Early Identification and Diagnosis, Funding Issues, Models of Care, Legal Rights Within the System, and Coordination of Medical Care.
Children's Hospital of Philadelphia
The Children’s Hospital of Philadelphia, Philadelphia, PA
Principal Investigator: Susan Levy, MD
This grant supports the creation of a database for the Regional Autism Center at the Children’s Hospital of Philadelphia. The Regional Autism Center treats one of the largest populations of children with autistic spectrum disorders in the nation, and provides comprehensive, coordinated, family-centered care, while continually striving to offer a repository of knowledge, support and guidance to affected families. The creation of a database is essential to strengthening the Center's research program and expediting collaboration and investigation of clinical and research questions facing these children and their families.
Children’s Hospital of Philadelphia - Regional Autism Center
The Hebrew College, Newton Centre, MA
Advancing the Jewish Special Education Program at Hebrew College
Despite the significant of the Bar/Bat Mitzvah in the Jewish life cycle, most synagogues are unprepared to accommodate children with special needs, and most tutors do not have the skills to teach them effectively. The NLM Family Foundation supports Hebrew College who, in partnership with Boston-based Special Needs program, Etgar L’Noar, serves children with moderate to severe special needs who are approaching Bar/Bat Mitzvah. These students have a variety of physical, cognitive, and/or behavioral impairments. Nearly half have diagnoses on the autism spectrum, in addition to other diagnoses in many cases. The program provides individual training to children and a supportive community of other Jewish students with special needs, while offering a living laboratory experience for Hebrew College student- teachers. Working with his/her student- teacher on an individualized program, each child has the opportunity to study, prepare, and practice the prayers, blessings, Torah reading, d’var torah, and other elements of his/her particular Bar/Bat Mitzvah. During group activities students practice their skills in a supportive environment. The curriculum also includes a tzedekah project for the class as a whole, so that these students, who have received so much help from others, can themselves experience the gift of giving. The students perform the ceremonies in their home communities so that they can become more integrated in the communities to which they belong.
Massachusetts Advocates for Children, Boston, MA
and Support of the Autism Special Education Legal Support
goal of this project is to provide training, technical assistance,
and advocacy services necessary to ensure that children
with autism receive equal educational opportunities. Goals
include: Providing parents with information about state-of-the-art
services and programs available to meet individual needs
of students with disabilities; Insuring that children with
autism receive special education services necessary to reach
their potential in areas impacted by their disability; Increasing
public awareness and understanding of the potential and
competency of individuals with autism, targeting policy
makers, media, educators, service providers, as well as
the general public. The Autism Special Education Legal Support
Center will accomplish these goals by: providing community-based
workshops for parents, educators, and medical professionals
regarding legal rights and range of service options available
for children with autism; providing a hotline to give legal
and technical assistance to families of children with autism;
training attorneys to increase representation of low-income
students with autism to ensure that children receive legally
mandated special education services; and providing information
to the media, the legislature, and other policy makers regarding
changes necessary to ensure children with autism receive
services that reflect their potential.
Massachusetts Advocates for Children
Massachusetts General Hospital, Boston, MA
Principal Investigator: Susan Santangelo, Sc.D.
Co-Investigators: Iain Fraser, MBCHB, D. Phil, Katherine Tsatsanis, Ph.D.
The Establishment of a Well-Characterized Cohort for Autism Studies at the Massachusetts General Hospital
This project will establish a well-characterized and documented patient sample and database that will allow investigators to begin a multidisciplinary, comprehensive program designed to elucidate underlying mechanisms important in the manifestation of autism. The investigators envision the establishment of a repository of genotypic and phenotypic information which will serve the needs of researchers interested in the neurobiology of the disorder. The patient sample and database will be developed from the patient population of the Learning and Developmental Disabilities Evaluation and Rehabilitation Service (LADDERS) program. In one year, 75 individuals with autism and their immediate family members who seek treatment at the LADDERS program will be recruited and expertly phenotyped with measures that will support a myriad of studies investigating the etiology of autism. A comprehensive database will be created that will contain all of the phenotypic and genetic information for these families. Both quantitative and qualitative phenotypes will be assessed for individuals with autism, their siblings and parents. All of the individuals with autism will be examined for evidence of gastrointestinal difficulties, immune dysfunction, and medical problems that may be associated with mitochondrial disorders. A permanent bank of cell lines will be established from recruited families to support gene mapping studies and DNA, RNA and protein level analyses in the future.
Massachusetts Institute of Technology, Cambridge, MA
Principal Investigator: Emilio Bizzi, M.D.
Improving the Communication Capabilities of People with Autism Who Use Assisted Typing Through the Use of Mechanical Devices
The goal of this project is to develop a system to improve the communication capabilities and eye-hand coordination of patients with autism. In general terms, the use of the system will be as follows: a set of letters (targets) will be presented sequentially or simultaneously on a screen. An eye-tracking system will record the position of the subject’s eyes as they converge on the target’s spatial location. With the help of an assistive (phantom) device the subject’s finger will be guided to the spatial position of the target. Depending upon the age and spelling ability of the subject, pictures may substitute letters presented on the screen. The system will be comprised of three parts: a) an eye-tracking system, b) a phantom device to which the subject’s finger will be attached and which will help guide them to touch the target, and c) a software interface that will couple the two systems. This system aims to improve subjects’ communication capabilities as well as subjects’ eye-hand coordination.
Nottingham Trent University, Milton Keynes, UK
Principal Investigator: Andy Grayson, Ph.D.
Eye-Tracking and Facilitated Communication
Facilitated communication (FC) is a strategy which aims to enhance communication skills by helping people learn to point or type. It is controversial when used by people with autism because it involves physical contact between the FC user and facilitator, making it difficult to determine who is responsible for the typing. Some peer-reviewed studies have concluded that the emergent language is being authored by the facilitator, while other peer reviewed studies have concluded that the emergent language is authored by the FC user. Some, but not all speech and language professionals maintain that FC is a useful strategy. This research will use fine-grained video analysis to measure typing-related behaviors in FC users and facilitators. By comparing the same FC users working with different facilitators, and facilitators working with different FC users, inferences about authorship can be drawn based on behavioral inconsistencies. If an FC user is typing, one would expect to see consistency in the way they type letters and words, irrespective of who is giving physical support. This project also explores the usefulness of eye-tracking technology as a means for enhancing understanding of FC. FC users will wear eye-tracking equipment while typing, which shows where they are looking at any given point in time.
State of the Art, Inc., Washington, DC
Support for the Distribution of "Autism Is A World" to US Public Libraries and Production of a Spanish Translation of the Film
Academy Award nominated documentary, "Autism Is A World", aired on CNN Presents on May 22, 2005. The purpose of this grant is to underwrite the distribution of free copies of "Autism Is A World" to 16,000 public libraries across the United States and the production of a Spanish translation of the film. For more information about "Autism Is A World", please visit the film's web page at www.autismisaworld.com.
State of the Art, Inc.
Syracuse University, Facilitated Communication Institute, Syracuse , NY
Principal Investigator: Douglas Biklen, Ph.D.
The NLM Family Foundation has supported the Facilitated Communication Institute for several years. Through the Core Funding Grant, the Strategic Planning Grant and the Lurie Scholarship Fund, the NLM Family Foundation supports the FC Institute's activities in facilitated communication training, documentation and demonstration, and reinitiates a strategic planning process to better focus the Institute for the next 5-10 years of work in the field of autism and inclusion. The Foundation also provided a grant to Dr. Biklen to support his work in collecting autobiographical accounts from people with autism who had been previously considered low functioning but now communicate fluently and some even independently with use of FC. Dr. Biklen has written a book of autobiographical accounts of seven individuals with autism published in 2005, entitled Autism and the Myth of the Person Alone .
TASH, Baltimore, MD
Fostering Support of a Full Range of Communication Methods and Empowering Users of Facilitated Communication and other Augmentative and Alternative Communication Methods
TASH is an international association of people with disabilities, their family members, and professionals advocating for inclusion of all people in all aspects of society. The aim of this project is to identify and overcome barriers that stand in the way of people with communication differences and difficulties self-directing their lives and becoming full participants in their communities and the disabilities rights movement. Project teams, including people with autism who have communicated using Facilitated Communication (FC) and TASH staff, will accomplish this goal by: 1) broadening the voice of Alternative and Augmentative Communication (AAC) users by building better connections with self-advocacy, advocacy and the disability community regarding communication rights; 2) building a comprehensive website which will provide resources on FC, including research articles, training information, and information on legislative action; 3) increasing the number of organizations that understand the importance of communication and accept as a valid, evidence-based practice the full range of AAC methods; 4) bringing AAC users and advocates to Washington, DC to participate in an organized public policy day; and 5) making Hill visits to educate elected officials about the issues regarding the need for research about and access to funding and services for AAC.
University of Cambridge, Cambridge, England
Principal Investigator: Lindsey Kent, MBChB., PhD. MRC Psych
Investigation of Imprinted Chromosomal Regions and Mitochondrial Haplotypes in Autism
Autism is a developmental condition that may impair social development, communication, and may be accompanied by narrow interests and repetitive activity. Twin and family studies demonstrate a genetic contribution to autistic spectrum disorders (ASD’s). Although substantial effort is aimed at identifying these susceptibility genes, there is no unequivocal evidence to implicate a particular gene. This study proposes two novel approaches to investigating possible genetic risk factors. Firstly, ASD’s are known to occur in a number of disorders which arise from individuals possessing extra genetic material such as chromosomal duplications. The overgrowth condition known as Beckwith Weidemann syndrome (BWS) can occur in individuals who inherit two copies of a part of chromosome 11 from their father. The researcher has recently found that a number of these BWS individuals also have autism, suggesting that an autism susceptibility gene may be present on chromosome 11, although may only be expressed when inherited from the father. Secondly, there is evidence from several case reports to suggest that variation in the mitochondrial genome may be associated with autism but the role of the mitochondrial genetic code has not been widely investigated in ASD’s. Mitochondria supply cells with sufficient energy for a wide range of cellular processes. Polymorphisms within mitochondrial genes may therefore have functional consequences on cellular functions. This study will investigate these mechanisms in 300 autism probands parent trios and 230+ Asperger syndrome trios, as well as a control sample in the mitochondrial studies.
University of Illinois, The Psychiatric Institute, Chicago , IL
Principal Investigator: Stephen Porges, Ph.D.
Stimulating Social Communication in Adolescents and Adults with Autism Spectrum Disorders: A Neurological Approach
The goal of this project is to demonstrate the efficiency and efficacy of the Listening Project, a biologically-based behavioral intervention derived from the Polyvagal Theory, on adolescent and adult individuals with Autism Spectrum Disorder. The Polyvagal Theory provides a neurobiological explanation for specific neural mechanisms associated with the spontaneous social behavior expressed by humans. This project is based on the premise that social behavior is a naturally occurring emergent property of the human nervous system. According to this model, positive social behavior is dependent on the nervous system being in a specific state. Intervention strategies that foster this state will have a positive impact on the social interaction skills of people with autism. The research program focuses on the development, evaluation, and application of this class of interventions in a cohort of adults with autism.
The Psychiatric Institute
University of Pittsburgh, Pittsburgh, PA
Principal Investigators: Nancy Minshew, M.D., Thomas Conturo, M.D., Ph.D.
Diffusion Tensor Tracking of Connectivity Abnormalities in Autism
Recent functional imaging studies (fMRI) have revealed a reduction in functional connectivity across cortical brain regions involved in language, problem solving, and social cognition; simple tasks showed normal connectivity. Structural brain studies have shown an increase in brain volume attributable largely to an increase in the outer white matter zone. This white matter connects immediately adjacent areas of cortex and makes longer distant connections between cortical regions within the same hemisphere. The corpus callosum, the major white matter pathway connecting the two hemispheres, is smaller in autism. This study will investigate white matter connections using a new method called diffusion tensor fiber tracking to map white matter pathways related to each of the major symptom areas of autism. The size, shape and density of these pathways in high functioning teens and adults with autism will be compared to matched normal controls and behavioral indices. This study will advance the understanding of connectivity in autism, pave the way for comparisons with functional connectivity, guide developmental neurobiologic studies, and provide an index for future cognitive rehabilitation strategies designed to enhance connectivity.
University of Washington CPEA and STAART Centers
Autism Neuroimaging Collaborative Research Meeting
Many autism research groups have neuroimaging research projects, which utilize magnetic resonance imaging for structural, functional, and metabolic imaging, included in their programs. Centers are currently using their own protocols for data acquisition and analysis and many of studies from these groups have yielded inconsistent results. The lack of consistency may result from relatively small sample sizes, differences in subject characteristics, differences in scan acquisition details, differences in fMRI task paradigms, and differences in data analysis techniques.
This meeting will provide the opportunity for researchers to discuss possible options for making the most meaningful use of data already collected at various sites and to plan for future studies whereby more consistent methods of data collection and analysis will be adopted by as many sites as possible. Researchers will also discuss development of the computational infrastructure that will be needed to support data-sharing among various groups, including the possibility of implementing a peer-to-peer neuroimaging network.
University of Washington Autism Center