Recent Autism Gastrointestinal research funded by NIH

24 Jul

There are many parent advocates asking for research into gastrointestinal disorders and autism. My own anecdotal observations have been that these same parent advocates are of the belief that no work is ongoing. There are a number of projects ongoing and I’ve tried in the past to make that point (What projects are being funded in autism research? Part 1: vaccines and GI issues). I found 14 projects, nearly $3M in 2010. I found 11 projects for $1.7M in 2009.

I thought it time to revisit this question. I’m using a different data source–the NIH RePORTER database. Because of that these projects are those funded by NIH. Other Federal groups can and do fund autism research. Also private organizations like Autism Speaks

Below are the projects I found for the past few years. There are projects on epidemiology, treatment and biology.

While I think that the funding agencies could do a better job informing the communities about these projects, I sincerely wish that the parent advocacy groups calling for this research would inform their members that it is going on. I am actually very curious as to why they have not done that.

MECHANISMS OF AUTONOMIC BRAINSTEM DEVELOPMENT ($243,000)

Brainstem and autonomic circuitry, though understudied in neurodevelopmental disorders, are implicated in pathophysiology and co-occurring medical conditions, such as gastrointestinal disturbances (GID). The goal of this R21 project is to fill this knowledge gap, based on significant preliminary data.

CASEIN KINASE 1 INHIBITORS FOR TREATMENT OF AUTISM $349,610

The overall goal of our program is to (1) identify CK1 [Casein Kinase 1] inhibitors suitable for development as therapeutic agents and (2) to use these agents to investigate the suitability of CK1 inhibitors for addressing specific behavioral features of the complex, multi-symptom disorder known as autism.

The CADDRE SEED studies are multiyear but I haven’t listed all the grants. So the amount is much higher than even the substantial sums noted below.

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $91,706

MD CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT, SEED PHASE II $1,600,000

CALIFORNIA CADDRE-SEED PHASE II $1,100,000

NC CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

COLORADO CADDRE STUDY TO EXPLORE EARLY DEVELOPMENT CADDRE_SEED II $1,100,000

PA-CADDRE: STUDY TO EXPLORE EARLY DEVELOPMENT (SEED) PHASE II $1,100,000

SEED will address hypotheses including: ASD phenotypic variation, including the pattern of clustering of core symptoms, timing of onset, cognitive status, and presence of medical and psychiatric co-morbidities; gastrointestinal features; genetic variation and interaction with environmental risk factors (GxE); infection, immune function, and autoimmunity factors; hormonal factors and maternal reproductive characteristics; and sociodemographic and lifestyle factors.

INVESTIGATING THE GUT MICROBIOME FOR NOVEL THERAPIES AND DIAGNOSTICS FOR AUTISM $558,136 (also funded in 2013 for $558,136)

Based on compelling preliminary evidence, this project aims to explore the potential connection between GI barrier defects and altered behavior in preclinical models of autism. Our long-term goal is to explore possible serum biomarkers for ASD diagnosis, and potentially develop a novel probiotic therapy for at least a subset of children with ASD with GI issues.

2013 projects

TREATMENT OF MEDICAL CONDITIONS AMONG INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS $488,568 (also, $339,591 in 2012, $264,726 in 2011, $578,006 in 2010, $535,209 in 2009, and $465,840 in 2008)

The life-long impairments in communication and social function are often complicated by the presence of medical comorbidities, including epilepsy, (and epileptiform discharges), gastrointestinal disturbances and sleep disorders.

REGULATION OF GASTROINTESTINAL NEUROMUSCULAR FUNCTION BY NIBP/NFKB SIGNALING $320,576 (and 2012 $343,747)

The proposed research is relevant to public health because the discovery of a novel function of NIBP/NFkB signaling in enteric neurons and glial cells is ultimately expected to increase the understanding of the pathogenesis of gastrointestinal diseases. It also shed light on the therapeutics for gastrointestinal inflammation and functional disorders.

ARE AUTISM SPECTRUM DISORDERS ASSOCIATED WITH LEAKY-GUT AT AN EARLY CRITIACAL PER $292,221 (and 2012 $302,820, and 2011 $302,820)

This project seeks to answer fundamental questions about the connection between early development of gastrointestinal (GI) problems (constipation, diarrhea, vomiting, etc.) and autism spectrum disorders (ASD)

From 2011

NEUROIMMUNOLOGIC INVESTIGATIONS OF AUTISM SPECTRUM DISORDERS (ASD) $264,726

A number of anecdotal reports have linked autism with gastrointestinal (GI) dysfunction; most notable among these are reports that autism is associated with “leaky gut” syndrome. Microbial translocation (MT) is the process by which bacteria or microbial byproducts permeate through the wall of the GI Tract (or other abnormally porous mucosal barriers) into the bloodstream. The microbial byproducts would then stimulate the immune system, which could have secondary effects on CNS functioning, or the byproducts could have a direct neurotoxic effect. We conducted assays of MT products in children with autism (from blood and CSF), as well as typically developing children (blood samples only).

and

Our ongoing phenotyping studies will be used to identify a cohort of children with autism who also have significant gastrointestinal symptoms in order to address this potentially important subgroup of patients.

A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES $156,634


By Matt Carey

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5 Responses to “Recent Autism Gastrointestinal research funded by NIH”

  1. Alan Packer July 25, 2014 at 18:24 #

    Matt, Just wanted to mention that SFARI is funding a very interesting project led by Ellen Li at Stony Brook University, “Autism, GI symptoms and the enteric microbiota”. We also supported, in part, some of the work in the recent Cell paper on CHD8 mutation and GI symptoms. We hope to fund more of this kind of work in the future. -Alan Packer (Senior Scientist, SFARI).

    • Sullivan (Matt Carey) July 25, 2014 at 19:13 #

      First off Alan–you guys rock! Simons, rocks. SFARI is the best source of autism science info hands down. Thank you all for what you are doing.

      I haven’t done as good a job as I might highlighting what is being funded and done in areas like GI. I figured the people more focused on this area would be watching but I don’t see those groups discussing this either. And, frankly, there’s some frustration from people who believe that there is no work going on in areas like GI and autism.

      One question I have in some of these studies is how does one control for diet? At least anecdotally, there is a lot of limited diet/picky eaters in the autistic population and I would naively expect this to result in differences in the microbiome. Not saying this would explain all the differences, but it seems like something that should either be explained or controlled for.

      • Alan Packer July 25, 2014 at 19:55 #

        Matt, thanks for the kind words. You raise an important question about diet in these GI microbiome studies. I believe there are some published data to suggest that gut microbiome changes in individuals put on particular diets and followed over time (high vs. low fat; high vs. low fiber) are actually modest compared to interindividual differences seen in the population. In any case, I believe Ellen Li is collecting data about diet in her study, and may be able to account for any confounding effects of picky eaters.

  2. Seth Bittker August 22, 2014 at 21:36 #

    Hi Matt,

    Thank you for highlighting this. You make a good point that it is easy to miss the work that is being done and we should applaud it. It seems to me that there is too little funding in this area though.

    In my opinion there is relatively too much research funding going into neurology, brain imaging, and especially behavioral research and psychological research on autism. We know that autism features specific behaviors by definition. It seems to me various studies to categorize behaviors or approaches to behavioral issues are unlikely to lead to any sort of a breakthrough.

    Ultimately behavior is dictated by what is going on in the brain. So one might assume studying neurology and the brain would be productive. I doubt it. We know based on past research quite a bit about neuronal over-connectivity and neuronal damage in autism. The question isn’t whether there is neuronal dysfunction: the question is what causes it?

    The cause is almost certainly the dysfunctional biochemistry. We look at kids with autism and control groups and we can see that the biochemistry is different. Measures of oxidative stress and endothelial damage are higher in autism, there is a Th2 skew to the immune system in autism, and there are higher levels of catecholamine derivatives in autism.

    What cuases these differences? It is almost certainly genetics combined the with environment and the bacteria in the digestive tract are a key component of the environment. Based on past research we know there are differences in the bacteria in the digestive tract of those with autism and controls.

    So I hope that those allocating funds will put greater emphasis on funding projects relating to biochemistry, the microbiome, immunology, and comparative epidemiology of autism and less emphasis on behavioral, physchological, neuronal, and brain research in autism.

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