New hope in autism, as top researchers study many possible

contributing causes.

Genes alone cannot account for the rapid rise in autism cases in the last couple decades. Top centers are studying immunological, environmental, infectious, toxic, and genetic factors. The predominant paradigm is no longer that the autism syndrome is a fixed, immutable genetic disorder.



JOHNS HOPKINS UNIVERSITY

http://www.neuro.jhmi.edu/neuroimmunopath/autism.htm

Why study neuroglial and immune reactions in autism?
Current evidence suggests that neurobiological abnormalities in autism are associated with changes in cytoarchitectural and neuronal organization that may be determined by genetic, environmental, immunological and toxic factors. Since neuroglia have central roles during brain development, cortical organization, neuronal function and immune responses, we hypothesize that neuroglia may contribute to the pathogenesis of autism in several ways:
Neuroglia may be dysfunctional during the process of neuronal organization and plasticity of cortical and subcortical structures, a change that may contribute to the neuropathological abnormalities observed in autism.
Neuroglia may react to extrinsic factors, such as systemic immune responses, toxins or infections, and produce disturbances in the CNS microenvironment that facilitate the development of immune mediated reactions.
Abnormal neuroglial activation may be present in autistic patients due to genetic susceptibility to inflammation, a change that can lead to abnormalities in neuronal-neuroglial interactions.
Neuroglial activation can trigger the development of cellular or humoral immune responses that lead to neuronal/neuroglial dysfunction.
Systemic immune responses may trigger abnormal pathogenic reactions in neuroglia.
Our experimental approaches include study of brain tissues obtained from patients with autism, determination of the profile of cytokines and chemokines and characterization of immune mediated reactions in cortical and subcortical regions of autistic brains. Further understanding of the role of neuroglia and immune reactions in the neurobiology of autism may contribute to the design of therapeutic interventions that minimize the neurological and behavioral abnormalities that occur in this disease.
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The Transcend Research Laboratory at Mass General/Harvard

http://www.mgh.harvard.edu/neurology/research/researchlab.aspx?id=1260

TRANSCEND’s partners work from a model of autism that describes a complex whole body condition with many treatable facets.
Brain as part of the body
We look at the brain not just as an information-processing computer but also as a physical organ that is part of the body.
We think that the way the brain processes sensory, emotional and social information is related to the health of the cells of the brain, which can be related to the health of cells in the body.
We think that changes in the way the brain processes sensory, emotional and social information might come from physical changes in the cells of the brain related to some kinds of physical illness in the body (especially immune problems), and not just from the brain developing differently before a baby is born.
Brain and body problems in autism and other neurodevelopmental disorders and how they develop
We suspect that the relationship of health problems and brain/behavior problems may develop in close relationship to each other.
Therefore we look at how brain and body problems develop early in autism and how these brain and body problems may relate to each other early on

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U.S. Department of Health and Human Services
Interagency Autism Coordinating Committee

http://iacc.hhs.gov/strategic-plan/2010/caused_prevented.shtml

The 2010 Interagency Autism Coordinating Committee Strategic Plan for Autism Spectrum Disorder Research

Although most scientists believe that risk factors for ASD are both genetic and environmental, there is considerable debate about whether potential environmental causes, genetic precursors, or interactions between genes and environmental factors should be the highest priority for research aimed at identifying the causes of ASD. To date, few studies have ruled in or ruled out specific environmental factors. There are reports of associations of ASD with exposure to medications, maternal antibodies, toxicants, and infections prenatally or postnatally, however these observations need to be the subject of additional study. It is still not known whether any specific factor is necessary or sufficient to cause ASD. Similar to other disease areas, advancing research on the potential role of environmental factors requires resources and the attraction of scientific expertise. Bringing this to bear on autism will help define the environmental factors to study, as well as the best approach for staging studies to examine environmental factors, interaction between factors, and between individual susceptibility and various environmental factors.

Short-Term Objectives
Coordinate and implement the inclusion of approximately 20,000 subjects for genome-wide association studies, as well as a sample of 1,200 for sequencing studies to examine more than 50 candidate genes by 2011. Studies should investigate factors contributing to phenotypic variation across individuals that share an identified genetic variant and stratify subjects according to behavioral, cognitive, and clinical features. IACC Recommended Budget: $43,700,000 over 4 years.
Within the highest priority categories of exposures for ASD, identify and standardize at least three measures for identifying markers of environmental exposure in biospecimens by 2011. IACC Recommended Budget: $3,500,000 over 3 years.
Initiate efforts to expand existing large case-control and other studies to enhance capabilities for targeted gene – environment research by 2011. IACC Recommended Budget: $27,800,000 over 5 years.
Enhance existing case-control studies to enroll racially and ethnically diverse populations affected by ASD by 2011. IACC Recommended Budget: $3,300,000 over 5 years.
New objective
Support at least two studies to determine if there are subpopulations that are more susceptible to environmental exposures (e.g., immune challenges related to infections, vaccinations, or underlying autoimmune problems) by 2012. IACC Recommended Budget: $8,000,000 over 2 years.
New objective
Initiate studies on at least 10 environmental factors identified in the recommendations from the 2007 IOM report "Autism and the Environment: Challenges and Opportunities for Research" as potential causes of ASD by 2012. Estimated cost $56,000,000 over 2 years.
Long-Term Objectives
Conduct a multi-site study of the subsequent pregnancies of 1,000 women with a child with ASD to assess the impact of environmental factors in a period most relevant to the progression of ASD by 2014. IACC Recommended Budget: $11,100,000 over 5 years.
Identify genetic risk factors in at least 50% of people with ASD by 2014. IACC Recommended Budget: $33,900,000 over 6 years.
Determine the effect of at least five environmental factors on the risk for subtypes of ASD in the pre- and early postnatal period of development by 2015. IACC Recommended Budget: $25,100,000 over 7 years.
Support ancillary studies within one or more large-scale, population-based surveillance and epidemiological studies, including U.S. populations, to collect data on environmental factors during preconception, and during prenatal and early postnatal development, as well as genetic data, that could be pooled (as needed), to analyze targets for potential gene/environment interactions by 2015. IACC Recommended Budget: $44,400,000 over 5 years.