Strategic Plan Objective Detail
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Question 2: Short-term Objective A  

$4,972,407.28
Fiscal Year: 2010

Green dot: Objective has greater than or equal to the recommended funding.2SA. Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010. IACC Recommended Budget: $9,800,000 over 4 years. (Fever studies to be started by 2012.)

Download 2010 Question 2: Short-term Objective A projects (EXCEL)
Note: Initial Sort is by Principal Investigator. Sorting by other columns is available by clicking on the desired column header.
Project Title Principal Investigator Institution
The pathogenesis of autism: Maternal antibody exposure in the fetal brain Diamond, Betty The Feinstein Institute for Medical Research
The effect of mercury and neuropeptide triggers on human mast cell release of neurotoxic molecules Theohardies, Theoharis Tufts University
Systematic characterization of the immune response to gluten and casein in autism spectrum disorders Alaedini, Armin Weill Cornell Medical College
Study of anti-neuronal autoantibodies in behavioral and movement disorders Cunningham, Madeleine University of Oklahoma Health Sciences Center
Regulation of inflammatory Th17 cells in autism spectrum disorder Littman, Dan New York University School of Medicine
Redox abnormalities as a vulnerability phenotype for autism and related alterations in CNS development Hepel, Maria State University of New York at Potsdam
Redox abnormalities as a vulnerability phenotype for autism and related alterations in CNS development James, Sandra Arkansas Children's Hospital Research Institute
Redox abnormalities as a vulnerability phenotype for autism and related alterations in CNS development Noble, Mark University of Rochester
Prostaglandins and cerebellum development McCarthy, Margaret University of Maryland, Baltimore
Project 2: Immunological susceptibility of autism Van de Water, Judy University of California, Davis
Primate models of autism Bauman, Melissa University of California, Davis
Primate models of autism Bauman, Melissa; Amaral, David University of California, Davis
Neurological diseases due to inborn errors of metabolism Pascual, Juan University of Texas Southwestern Medical Center
Molecular pathways involved in oxidative stress and leaky gut impairment in autism spectrum disorders Antonucci, Nicola University of Naples
Mechanisms of mitochondrial dysfunction in autism Shoffner, John Georgia State University
Maternal infection and autism: Impact of placental sufficiency and maternal inflammatory responses on fetal brain development Palmer, Theo Stanford University
Maternal immune activation, cytokines, and the pathogenesis of autism McAllister, A. Kimberley University of California, Davis
Is autism a mitochondrial disease? Giulivi, Cecilia University of California, Davis
Influence of the maternal immune response on the development of autism Ponzio, Nicholas University of Medicine & Dentistry of New Jersey
Influence of oxidative stress on transcription and alternative splicing of methionine synthase in autism Muratore, Christina Northeastern University
Influence of maternal cytokines on activation of the innate immune system as a factor in the development of autism Ponzio, Nicholas University of Medicine & Dentistry of New Jersey
Influence of maternal cytokines during pregnancy on effector and regulatory T helper cells as etiological factors in autism Ponzio, Nicholas University of Medicine & Dentistry of New Jersey
Immune molecules and cortical synaptogenesis: Possible implications for the pathogenesis of autism McAllister, A. Kimberley University of California, Davis
How does IL-6 mediate the development of autism-related behaviors? Hsiao, Elaine California Institute of Technology
Gene-environment interactions in the pathogenesis of autism-like neurodevelopmental damage: A mouse model Pletnikov, Mikhail Johns Hopkins University School of Medicine

Objective Cumulative Funding Table

IACC Strategic Plan Objective 2008 2009 2010 2011 2012 Total
Support at least four research projects to identify mechanisms of fever, metabolic and/or immune system interactions with the central nervous system that may influence ASD during prenatal-postnatal life by 2010 (Fever studies to be started by 2012).

IACC Recommended Budget: $9,800,000 over 4 years
2.2
$3,377,568
18 projects

2.S.A
$3,584,634
30 projects

2.S.A
$4,972,407
37 projects

2.S.A
$2,013,417
25 projects

2.S.A
$3,049,827
26 projects

$16,997,853
2.S.A. Funding: The recommended budget for this objective was met.

Progress: Many projects were funded in this area (approximately 20-30 per year), but the field is still developing, and emphasis on this objective should continue in the future. Scientific advances have been made in linking maternal innate immune function and immune-system challenge to aspects of ASD. Methodological advances in the field include the development of animal models for study of the role of the immune system in ASD and PET ligands for imaging microglial activation.

Remaining Gaps, Needs and Opportunities: There is a need for a well-designed, multi-site clinical study of clinical effects of fever and to develop standard measures of fever and behavioral/cognitive outcomes. Questions about fever could be integrated into funded epidemiological studies. There is also interest in further work on metabolic and mitochondrial issues, but in order for this work to be done, there is a need for validation and standardization of measures for assessment of oxidative stress and mitochondrial function. More guidance is needed on the key questions for this field to answer – a workshop to define these methodologies may be helpful. One of the key questions is to determine whether it is the body temperature associated with fever or some consequence of immune activation and production of the febrile state that leads to amelioration of cognitive function.