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Press Release: Common gene variants account for most genetic risk for autism

23 Jul

This press release is from NIH: Common gene variants account for most genetic risk for autism

Common gene variants account for most genetic risk for autism
Roles of heritability, mutations, environment estimated – NIH-funded study

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Most of the genetic risk for autism comes from versions of genes that are common in the population rather than from rare variants or spontaneous glitches, researchers funded by the National Institutes of Health have found. Heritability also outweighed other risk factors in this largest study of its kind to date.

About 52 percent of the risk for autism was traced to common and rare inherited variation, with spontaneous mutations contributing a modest 2.6 percent of the total risk.

nimh-20_l

The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations in the genetic code shared by many people. These and other (unaccounted) factors dwarfed contributions from rare inherited, non-additive and spontaneous (de novo) genetic factors. Source: Population-Based Autism Genetics and Environment Study
“Genetic variation likely accounts for roughly 60 percent of the liability for autism, with common variants comprising the bulk of its genetic architecture,” explained Joseph Buxbaum, Ph.D., of the Icahn School of Medicine at Mount Sinai (ISMMS), New York City. “Although each exerts just a tiny effect individually, these common variations in the genetic code add up to substantial impact, taken together.”

Buxbaum, and colleagues of the Population-Based Autism Genetics and Environment Study (PAGES) Consortium, report on their findings in a unique Swedish sample in the journal Nature Genetics, July 20, 2014.

“Thanks to the boost in statistical power that comes with ample sample size, autism geneticists can now detect common as well as rare genetic variation associated with risk,” said Thomas R. Insel, M.D., director of the NIH’s National Institute of Mental Health (NIMH). “Knowing the nature of the genetic risk will reveal clues to the molecular roots of the disorder. Common variation may be more important than we thought.”

Although autism is thought to be caused by an interplay of genetic and other factors, including environmental, consensus on their relative contributions and the outlines of its genetic architecture has remained elusive. Recently, evidence has been mounting that genomes of people with autism are prone to harboring rare mutations, often spontaneous, that exert strong effects and can largely account for particular cases of disease.

More challenging is to gauge the collective impact on autism risk of numerous variations in the genetic code shared by most people, which are individually much subtler in effect. Limitations of sample size and composition made it difficult to detect these effects and to estimate the relative influence of such common, rare inherited, and rare spontaneous variation.
Differences in methods and statistical models also resulted in sometimes wildly discrepant estimates of autism’s heritability – ranging from 17 to 50 percent.

Meanwhile, recent genome-wide studies of schizophrenia have achieved large enough sample sizes to reveal involvement of well over 100 common gene variants in that disorder. These promise improved understanding of the underlying biology – and even development of risk-scores, which could help predict who might benefit from early interventions to nip psychotic episodes in the bud.

With their new study, autism genetics is beginning to catch up, say the researchers. It was made possible by Sweden’s universal health registry, which allowed investigators to compare a very large sample of about 3,000 people with autism with matched controls. Researchers also brought to bear new statistical methods that allowed them to more reliably sort out the heritability of the disorder. In addition, they were able to compare their results with a parallel study in 1.6 million Swedish families, which took into account data from twins and cousins, and factors like age of the father at birth and parents’ psychiatric history. A best-fit statistical model took form, based mostly on combined effects of multiple genes and non-shared environmental factors.

“This is a different kind of analysis than employed in previous studies,” explained Thomas Lehner, Ph.D., chief of NIMH’s Genomics Research Branch. “Data from genome-wide association studies was used to identify a genetic model instead of focusing just on pinpointing genetic risk factors. The researchers were able to pick from all of the cases of illness within a population-based registry.”

Now that the genetic architecture is better understood, the researchers are identifying specific genetic risk factors detected in the sample, such as deletions and duplications of genetic material and spontaneous mutations. Even though such rare spontaneous mutations accounted for only a small fraction of autism risk, the potentially large effects of these glitches makes them important clues to understanding the molecular underpinnings of the disorder, say the researchers.

“Within a given family, the mutations could be a critical determinant that leads to the manifestation of ASD in a particular family member,” said Buxbaum. “The family may have common variation that puts it at risk, but if there is also a de novo [spontaneous] mutation on top of that, it could push an individual over the edge. So for many families, the interplay between common and spontaneous genetic factors could be the underlying genetic architecture of the disorder.”

New Study: Most genetic risk for autism resides with common variation

23 Jul

A new large study on autism genetics just came out: Most genetic risk for autism resides with common variation. The study is in Nature Genetics, one of the top journals.

The study is the latest in the evolved view of autism genetics. Contrary to political statements made by some groups, autism genetics is not about searching for a single “autism gene”. Here’s a quote from the CNN Blog that makes this clear:

Chris Gunter, an autism researcher at the Marcus Autism Center and professor at the Emory University School of Medicine, says the findings of this study are similar to those reported in other studies.

“There is no one gene for autism,” Gunter said. “Instead there are many different genetic variations which each contribute a little bit to the risk of developing the group of symptoms we diagnose as autism.”

No single autism gene. You might carry one or more genes which are associated with autism and not be autistic. But the more you have, the more your risk goes up. It may be linear: each variant has a “score” and you add them up and if your score is very high, you are autistic. Or it may be nonlinear: some genes in combination may create a greater risk than the sum of their individual risks. I don’t think they understand or have cataloged the genes well enough to say.

The researchers in this current paper are estimating about 60% of autism risk is genetic. Here’s a graphic showing the breakdown of the various risks–different types of genes (common genes that are inherited, rare genes that are inherited, new (de novo) mutations, etc.):

nimh-20_l

What does this mean for the future of autism research? It means that continuing to look at both genetics and environmental risk factors is valuable. As I’ve said before, from my perspective if autism risk is 10% genetic or 90% genetic, you still need to apply resources to both genetics and environmental risk factors.

Now to answer the more mundane questions. What does this mean for the vaccine epidemic? You can’t have a genetic epidemic (not really true, but good enough for this discussion)! This doesn’t fit with the idea that about 99% of autism is now caused by vaccines.

Yep. These data are yet another reason why your idea doesn’t work.

But isn’t this just blaming the mothers?

I’m always amazed when that argument comes up on autism genetics. And, yes, it does come up. Your children’s genetic makeup is neither a source of pride nor of blame. You really didn’t have any say in the matter. You didn’t create nor change your genes, how can you be blamed for the genes that your child inherits?

Won’t genetic research lead to aborting babies?

Maybe. If it does, it will be much different than the current situation with Down Syndrome. Autism doesn’t have many examples of single-genes, as this study points out. There have already been groups claiming to be working on tests involving multiple genes and autism risk scores.

Does this mean that the story is finished? That we have the last answer about how much risk is genetic and how much is environmental?

No. There will be more papers and more estimates. These are tough questions and knowledge evolves.

Here is the paper’s abstract:

A key component of genetic architecture is the allelic spectrum influencing trait variability. For autism spectrum disorder (herein termed autism), the nature of the allelic spectrum is uncertain. Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse. At issue is how much of an impact relative to rare variation this common variation has. Using a unique epidemiological sample from Sweden, new methods that distinguish total narrow-sense heritability from that due to common variation and synthesis of results from other studies, we reach several conclusions about autism’s genetic architecture: its narrow-sense heritability is ∼52.4%, with most due to common variation, and rare de novo mutations contribute substantially to individual liability, yet their contribution to variance in liability, 2.6%, is modest compared to that for heritable variation.


By Matt Carey

Is Boyd Haley resurrecting OSR#1 as a chelator?

22 Jul

Boyd Haley was a professor of chemistry who was very active in the failed thimerosal-causes-autism movement. He earned extra notoriety for trying to coin the phrase “mad child disease” (yes, a variation of mad cow disease) for autistic children. He also found notoriety for marketing a synthetic chemical as a “nutritional supplement”, calling it OSR#1. Prof. Haley is certainly persistent. He’s working on a clinical trial.

How did this come to pass? Well, one of the professors in Prof. Haley’s department found that a certain compound could effectively treat mining waste, removing mercury. Given his own interests, Mr. Haley started a company with an investor with the intent to bring this chelator to the public. The chelators used in medicine today were developed for lead and have been expanded to also treat mercury. I.e. there is no mercury specific chelator and this new compound would fill that gap.

All well and good, but in his zeal to bring this product to market, Prof. Haley cut a few corners. Chelators are drugs. The compound he was working on was synthetic. But Prof. Haley chose to rush the product to market as a “nutritional supplement”. Instead of calling it a chelator, he called it OSR#1. OSR standing for “oxidative stress relief”. Mr. Haley skipped the process to prove that his drug was safe and effective. Supplements have a much lower standard for safety and efficacy testing.

The FDA was not fooled. Mr. Haley and his company were given a warning letter which pointed out that the compound is not a supplement, it is a drug:

Your firm markets OSR#l as a dietary supplement; however, this product does not meet the definition of a dietary supplement in section 201(ff) of the Act, 21 U.S.C. § 321(ff). To be a dietary supplement, a product must, among other things, “bear[ ] or contain[ ] one or more … dietary ingredients” as defined in section 201(ff)(1) of the Act, 21 U.S.C.§ 321(ff)(1). Section 201 (ff)(1) of the Act defines “dietary ingredient” as a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract or combination of any dietary ingredient from the preceding categories. The only substance listed as a dietary ingredient on the labeling of OSR#1 is N1,N3-bis(2-mercaptoethyl)isophthalamide. N1,N3-bis(2mercaptoethyl) isophthalamide is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, N1,N3-bis(2-mercaptoethyl)isophthalamide is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. Thus, because OSR#1 does not bear or contain a dietary ingredient as defined in section 201(ff)(1) of the Act, this product does not qualify as a dietary supplement under section 201(ff) of the Act.

Also that the company was making claims that the drug could treat medical conditions and that the labeling was misleading in this regard. Further, that the toxicity was not adequately tested nor reported.

Your website states that” [s]ome reports of temporary diarrhea, constipation, minor headaches have been reported but these are rare and the actual causes are unknown,” as well as “OSR#1 is without detectable toxicity” and “OSR#1® … has not exhibited any detectable toxic effects even at exceptionally high exposure levels.” However, animal studies that you conducted found various side effects to be associated with OSR#1 use, including, but not limited to, soiling of the anogenital area, alopecia on the lower trunk, back and legs, a dark substance on lower trunk and anogenital area, abnormalities of the pancreas, and lymphoid hyperplasia. Based on these animal studies and side effects known to be associated with chelating products that have a similar mechanism of action to OSR#1, we believe the use of your product has the potential to cause side effects, and the before-mentioned website statements falsely assert that the product does not have the potential to cause side effects. Therefore, these statements render your product’s labeling false or misleading. As such, OSR#1 is misbranded under section 502(a) of the Act, 21 U.S.C. § 352(a).

That was in 2010. Prof. Haley and his company are now back, trying to get a clinical trial started on their compound. Essentially, they are trying to do what they should have done in the first place: get proper approval for a drug. An article in Chemical & Engineering News discusses this effort. Actually, it’s part of the cover story, “Building Pharma Molecules”

buildingpharma

The story on Mr. Haley’s Company, CTI Science, has contracted with another company, PCI Synthesis, to manufacture the new compound.

haley2

The article is, well, a bit of a sales pitch and gets a few facts wrong. There’s a bit of spin on the FDA warning letter, for example:

“The effort to develop the compound as a mercury poisoning therapy accelerated in 2010 when the company received notification from FDA that it couldn’t market NBMI as a nutritional supplement until it underwent the full drug approval process”.

As we’ve just seen above, the compound is not a nutritional supplement at all. It needs the drug approval process because it is a drug.

The CEO of PCI is quoted as stating:

“The main starting material is cysteamine hydrochloride, which is basically an amino acid and found naturally. So it has attributes that could qualify it as a natural product.”

Which was part of the sales pitch for the OSR#1 in the old days and, again, the FDA disagreed. Just because something is synthesized from a natural product, that doesn’t make it a natural product. Otherwise there would be no synthetic products at all. Everything at some level comes from a natural product.

The article discusses how to qualify for a clinical trial the product must meet current Good Manufacturing Practices (cGMP). The article states:

The primary challenge was the removal of impurities to a level that meets cGMP standards

Think about that a moment. Apparently OSR#1 was sold with more impurities than would meet this standard–a standard for food and dietary supplements.

The article notes that, yes, this compound was sold as a product at one time

Sales to date: $1.5 million, as a nutritional supplement

$1.5M in sales. And the only reason it wasn’t higher was because the FDA stepped in. It was only out for about a year, as I recall.

I found this statement interesting, from the Wikipedia page for the compound:

In animal experiments, the amount of mercury in brain tissue was not increased, but also not decreased

So, even if you believe in the failed mercury hypothesis. What exactly were you supposed to get from this compound? I somehow doubt that even the strong believers in the mercury hypothesis think that removing mercury from, say, your liver will cure autism.

It does seem that Mr. Haley and his company are doing some of the right things now. Show that this drug is safe and effective for its intended purpose: chelation. There are some problematical statements that they may market this not as a drug but as a nutritional supplement, which is a non-starter.


By Matt Carey

Robert Kennedy, where did you go wrong? And I’m not talking about thimerosal.

22 Jul

Robert Kennedy is one of the Kennedy’s. He also is known within the autism communities for his irresponsible and flawed “Deadly Immunity” article which appeared in Rolling Stone and Salon.com and which fueled much of the conspiracy theory mindset in a generation of autism parents. That was almost 10 years ago. A year or so back, Mr. Kennedy appeared at the AutismOne parent convention talking about thimerosal again. It’s hard to find a more receptive audience for his message. AutismOne is a staunch supporter of failed ideas like thimerosal and MMR cause autism. AutismOne is also a place that promotes the ideas that one can cure autism by chemically castrating disabled children, or making disabled children drink bleach or take bleach enemas until they pass their intestinal mucosa (which are relabeled as worms) and more.

If readers will indulge me, let me shift to addressing Mr. Kennedy:

While multiple outlets are taking turns pointing out that you have taken a very irresponsible stance on vaccines, I’ll just ask: Mr. Kennedy, did you spend any time looking around AutismOne? If so–why the hell have you not come forward to distance yourself from the junk science that goes on there? Why the hell did you lend your family’s name to that operation? Your family basically built the special education system in our country. The National Institute of Child Health and Human Development is named for a relative of yours. And you are loaning that name to a convention where the keynote speaker abuses autism parents? Have you sunk so low that you are lending your family’s credibility to Andrew Wakefield?

If you were unaware of what AutismOne is, shame on you for lending your name. If you are aware of these goings on, and don’t distance yourself, your stance on thimerosal is the least of your problems.


By Matt Carey

Environmental risk factor related research funded by the NIH in 2014

18 Jul

There is a great interest from some in the autism parent community for environmental risk factor research. There is also a belief that this work is not being performed. While the amount of environmental risk factor research is less than the IACC has advised be performed (a point I made in my first IACC meeting), the amount of attention to environmental risk factors has been increasing.

Given this, I thought it would be interesting to see what projects and how many have been funded by the NIH this year (I believe they work on a fiscal year ending Sept. 30, so we have much but not all of the 2014 information available). I used the NIH Reporter website and did a very unscientific search for autism and environment, autism and risk and similar searches.

Below are the funded projects I’ve found. Some are directly on topic. Some more peripherally. And I know I’ve left some out (some on purpose–like Zebrafish studies–and some I missed). I think there are 33 projects below. Something like $20M. Keep in mind, not all Federally funded autism research goes through the NIH and not all autism research is Federally funded.

As I like to point out in these articles, you won’t find this information on the websites of the autism organizations which claim to be focused on environmental risk factor research. In fact, you are more likely to find statements that there is no such research ongoing or it is being blocked.

Here’s a quote from Sallie Bernard of SafeMinds, a quote that was repeated by Congressman Posey at a hearing held last year on autism:

“By ignoring the environmental component to autism, the government and scientific community have made a massive strategic error, wasting enormous amounts of money and time in mostly fruitless genetics-only research that has not helped us stop new cases of autism or helped people living with severe autism”

I think one can argue that more investment should be made. But “ignoring”? I realize that very few people will go to NIH Reporter and search for these projects. But I expect accuracy from those claiming to lead the autism community and acting as though they know the research landscape on autism and the environment.

I was going to ignore the “fruitless” comment above, but I just can’t. I sat on the subgroup writing the IACC’s updates on risk factor research in the Strategic Plan (question 3). As part of that I had the honor of working with some excellent researchers, both on the genetics and the environmental side. If I may be so bold as to relate what I heard in those discussions: I never heard these researchers claim that the genetics research was “fruitless”. Quite the opposite. Was there a strong sense that environmental risk factor research could be better funded? That was certainly my take away. And I agree. My predecessors on the IACC wrote a Plan that called for more research in this area.

That said, I am reminded of my favorite old saying

There’s more politics in science than science in politics.

Except quite frankly, I don’t think the message that environmental risk factor research is being “ignored” and “fruitless” has anything to do with science. It’s just politics.

Here’s that list of funded research (in no particular order):

POPULATION-BASED AUTISM GENETICS & ENVIRONMENT STUDY $655,813

PROSPECTIVE EVALUATION OF AIR POLLUTION, COGNITION, AND AUTISM FROM BIRTH ONWARD $545,679

PESTICIDE EXPOSURE AND CHILDHOOD AUTISM $184,503

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN $231,692

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

ANTECEDANTS SEQUELAE OF CHILDHOOD ONSET DISEASE $432,000

MITOCHONDRIAL DYSFUNCTION DUE TO ABERRANT MTOR-REGULATED MITOPHAGY IN AUTISM $183,568

PRENATAL AND NEONATAL BIOLOGIC MARKERS FOR AUTISM $784,863

AUTISM RISK, PRENATAL ENVIRONMENTAL EXPOSURES, AND PATHOPHYSIOLOGIC MARKERS $1,793,611

THE ROLES OF ENVIRONMENTAL RISKS AND GEX IN INCREASING ASD PREVALENCE $537,756

METHYLOMIC AND GENOMIC IMPACTS OF ORGANIC POLLUTANTS IN DUP15Q SYNDROME $341,921

EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II $564,795

EARLY PREGNANCY STRESS PROGRAMMING OF OFFSPRING EMOTIONALITY $396,000

GENOME-WIDE IDENTIFICATION OF VARIANTS AFFECTING EARLY HUMAN BRAIN DEVELOPMENT $413,630

EPIGENETIC AND TRANSCRIPTIONAL DYSREGULATION IN AUTISM SPECTRUM DISORDER $531,208

EPIGENETIC INFLUENCE ON THYROID HORMONE ACTION IN THE BRAIN AND ON BEHAVIOR $391,250

MATERNAL ADVERSITY AND EPIGENETIC AND BEHAVIORAL PROGRAMMING ACROSS GENERATIONS $583,246

EXPLORING INTERACTIONS BETWEEN FOLATE AND ENVIRONMENTAL RISK FACTORS FOR AUTISM $118,717

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

SEX-DEPENDENT MICROGLIAL COLONIZATION AND VULNERABILITY TO A NEONATAL INFECTION $272,270

PRENATAL SEX STEROIDS, BISPHENOL A, PHTHALATES, AND SEXUALLY DIMORPHIC BEHAVIORS $244,996

ENVIRONMENT, IMPRINTING, AND NEURODEVELOPMENT $799,726

IN UTERO ANTIDEPRESSANT EXPOSURES AND RISK FOR AUTISM $348,000

SEX DIFFERENCES IN DEVELOPING MICROGLIA: IMPLICATIONS FOR SYNAPTIC PRUNING $392,500

ARE ENDOCRINE DISRUPTING COMPOUNDS ENVIRONMENTAL RISK FACTORS FOR AUTISM? $237,750

THE EFFECT OF MATERNAL OBESITY AND INFLAMMATION ON NEURONAL AND MICROGLIAL FUNCTI $78,250

TRANSCRIPTIONAL AND EPIGENETIC SIGNATURES OF HUMAN BRAIN DEVELOPMENT AND AUTISM $1,542,279

PROJECT 2: THE IMPACT OF ASSISTED REPRODUCTIVE TECHNOLOGIES ON THE LONG-TERM EPI $266,000

PRENATAL FACTORS AND RISK OF AUTISM IN A FINNISH NATIONAL BIRTH COHORT $579,293

One last note: I don’t see funding for the EARLI network. That strikes me as a shame.


By Matt Carey

Note: I serve as a public member to the IACC but all statements are my own.

More of that vaccine/autism research that doesn’t exist

17 Jul

There are some parents who want research on vaccines and autism. I may not agree that this is the best way to spend our limited resources, but there’s no denying that this group exists and is very vocal. One thing that surprises me is that these parents appear to be unaware of vaccine/autism research that is ongoing. Not just the studies that come out that show us over and over again that autism risk is not increased by vaccines. But other projects. Biology. Studies on regression. And more. I pointed out recently that using NIH Reporter, one can find a number of projects on autism and vaccines or autism and mercury.

But NIH is not the only Federal agency funding autism research. And there are private funders as well. As I mentioned in my previous article, another place to look for funded research projects is the IACC/OARC Autism Spectrum Disorder Research Portfolio Analysis Web Tool as this includes work the various groups represented on the IACC–both Federal and Private. Unfortunately, this tool only has 2008, 2009 and 2010 projects (had the GAO not required OARC to provide a lot of information last year, perhaps this tool would be updated by now. But such is the government.) But, even with this limitation in years, let’s see what projects come up with searches for vaccines or mercury. I’ll give the titles first, and then the abstracts for these projects below.

It’s understandable that parent advocates are not aware of these projects. I’ve written about this before (“What projects are being funded in autism research? Part 1: vaccines and GI issues”) but I think it’s safe to say that parents who believe in the vaccine/autism connection do not frequent Left Brain/Right Brain. There are places on the web that carry that message (for example, the Age of Autism blog and the sites of the organizations that sponsor it). They aren’t telling their constituencies about the ongoing research efforts. As an example, as I was finishing this article, SafeMinds came out with a letter discussing how no work is being performed on vaccines and autism.

Again, this list is only for 2008, 2009 and 2010. More recent projects from NIH were discussed here.

Vulnerability phenotypes and susceptibility to environmental toxicants: From organism to mechanism (funded by Autism Speaks)

Evaluation of the immune and physiologic response in children with autism following immune challenge (funded by Autism Speaks)

Vaccination with regression study (funded by Autism Speaks)

Vaccine safety datalink thimerosol and autism study (Federally Funded)

Analysis of developmental interactions between reelin haploinsufficiency, male sex, and mercury exposure (Funded by Autism Speaks)

MeHG stimulates antiapoptotic signaling in stem cells (Federally funded: DoD)

Etiology of autism risk involving MET gene and the environment (Funded by Autism Speaks)

Epidemiological research on autism in Jamaica (Federally Funded, NIH)

investigation on the potential harmful effects of mercury in the nonhuman primate (Funded by SafeMinds)

Investigating the effect of mercury on ASD, AD and ASD regression (Funded by SafeMinds)

The effect of mercury and neuropeptide triggers on human mast cell release of neurotoxic molecules (Funded by SafeMinds)

Does mercury and neurotension induce mitochondrial DNA release from human mast cells and contribute to auto-immunity in ASD? (Funded by SafeMinds)

Toxicant-induced autism and mitochondrial modulation of nuclear gene expression (Federally Funded: DoD)

Below are the abstracts for these research projects.

Vulnerability phenotypes and susceptibility to environmental toxicants: From organism to mechanism (funded by Autism Speaks)

One hypothesis regarding the association between genetic changes, environmental factors and autism is that many mutations or polymorphisms make the organism more vulnerable to later exposure in some individuals. Called the “vulnerability phenotype”, the Noble lab hypothesizes that one potential unifying theme of the vulnerability phenotype of children with ASD is that they are more oxidized. This elevated oxidation state has been shown to be sufficient to cause dramatic changes in cellular function. In this project, Dr. Noble will test the hypotheses that genetically-based differences in oxidative status are associated with differences in vulnerability to physiological stressors in vitro and in vivo, with even greater increases in vulnerability to combinations of physiological stressors. Specifically, thimerosal and other vaccine adjuvants will be studied. The second part of the study will determine if these effects on a novel regulatory pathway called redox/Fyn/c-Cbl is a necessary mechanistic convergence for increases in vulnerability caused by a more oxidized metabolic status. These results will provide a better understanding of the biochemical effects and mechanisms of possible toxicity of vaccines and vaccine additives. What this means for people with autism: These studies will initially focus on the combination of vaccine additives, but then examine whether a background genetic vulnerability phenotype affects the response to these additives. The results would provide new targets for intervention against the adverse effects of increased oxidative status in children with autism.


Evaluation of the immune and physiologic response in children with autism following immune challenge
(funded by Autism Speaks)

The overall goal of this proposal is to address immune function in children with autism, including the response to vaccine challenge, and how that relates to behavior. Evidence suggests that autism is associated in some cases with altered immune function, but the response of the immune system in children with autism to specific immune challenges, such as vaccines, has not been investigated directly. While it has been reported that some children with autism respond poorly following vaccination with symptoms ranging from rash, diarrhea, irritability, seizures, and loss of skills, no careful, thorough approach has been undertaken to fully characterize this issue, both at the biology and behavior level. We propose to use our current CHARGE (Childhood Autism Risks from Genetics and the Environment) and Autism Phenome Project (APP) study population to address this critical issue. The overall approach would include an examination of the immune response to both viral and bacterial vaccines in children with autism, as compared to typically developing age-matched controls, in real time following vaccination at 5 years of age. Vaccines have advantages for directly studying the immune response as they provide a known, scheduled immune challenge, whose dose is well characterized – making it possible to collect and interpret immune response data at the time that it occurs. Therefore, we think that exposure to an immune challenge with vaccine would result in an increase in inflammation compared to controls in a subpopulation of children with autism. However, we also anticipate that some children will respond to vaccine challenge differently, depending on form of the vaccine, i.e. viral vs. bacterial. Thus, we propose to address the issue of immune function in children with autism through a careful analysis of the immune system, medical and mitochondrial issues, and behavioral response to both viral and bacterial vaccines.

Vaccination with regression study (funded by Autism Speaks)

A major challenge to studying autism with a suspected vaccine-related regression is identifying children with acute regressive-type symptoms following MMR vaccination; there are no specific codes, tests, or procedures that identify this occurrence with a high degree of specificity. This study will explore the Kaiser Permanente electronic databases to ascertain whether we can identify children with regressive type autism and identify the timing of the regression in relation to the period directly following MMR vaccination. In order to see if identification of regressive autism from medical records is possible, the investigators will attempt to identify children vaccinated with MMR who then abruptly undergo a ‘cluster’ of visits, tests, and/or procedures in the time period directly following vaccination. The researchers feel that there may be a number of children who receive a diagnosis (such as ‘prolonged crying’) in the emergency department on the day after vaccination, followed shortly thereafter (1-2 days later) by another set of diagnoses (such as ‘fever’ & ‘irritability’) in the pediatric office or other outpatient department, and then receive either diagnostic or laboratory tests indicating (at least) a moderate degree of severity of concern, such as CT scans, metabolic testing, or referral to neurology. If this study is successful in using medical databases to identify a specific group of children with demonstrable autism-related regression that clearly follows vaccination, it may point to the feasibility of further studies concentrating on this specific population.

Vaccine safety datalink thimerosol and autism study (Federally Funded)

The Thimerosal and Autism Study is a case-control study conducted in three U.S. managed care organizations (MCOs). Data collection began in 2005 and took three years to complete. In this study, children who were diagnosed with autism were matched with control children. The autism diagnosis of the case samples was confirmed by a standardized clinical assessment protocol. Vaccination histories and information on other potential confounding factors were confirmed by reviewing the medical records for all children. In addition, the mothers of both cases and matched controls were interviewed.

Analysis of developmental interactions between reelin haploinsufficiency, male sex, and mercury exposure (Funded by Autism Speaks)

This project will investigate the role of three separate factors in an animal model of autism spectrum disorder: a) genetic susceptibility, b) hormonal environment, and c) possible environmental triggers. A mouse model with a mutation of the reelin gene, implicated in autism spectrum disorders, will be studied after exposure to methyl and ethyl mercury. Both behaviors and neuropathological endpoints will be explored. Finally, the role of endogenous sex hormones will be examined by eliminating the testosterone “surge” around the time of puberty. The individual effects of each will be examined, as well as the interaction of the three components (genetic liability, environmental exposure, hormonal influences) to determine gene x environment interactions. What this means for people with autism: This study will use a unique design to study multiple factors in the etiology of autism spectrum disorder in a mouse model, isolating and combining factors which previously have been implicated in the pathophysiology and behavioral phenotype.

MeHG stimulates antiapoptotic signaling in stem cells (Federally funded: DoD)

This project is a study of the antiapoptotic effect of low concentration of methly mercury and cadmium in cells.

Etiology of autism risk involving MET gene and the environment (Funded by Autism Speaks)

Two independent lines of evidence indicate that the maternal immune system and a functional genetic variant contribute to autism spectrum disorder (ASD) risk. Here, the Van De Water lab will partner with scientists at Vanderbilt University to examine whether these two seemingly unrelated contributions may converge to define a unique ASD susceptibility. Preliminary evidence collected by the Van De Water lab indicates an association between the Mesenchymal epithelial transition factor (MET) gene ‘C’ type, which reduces MET protein expression, and the presence of specific maternal anti-fetal brain autoantibodies. This relationship suggests that this as a pathway for production of the maternal autoantibodies, leading to a gene x environment interaction underlying ASD susceptibility. The next line of experiments will examine the relationship in an even larger sample and assess the functional effect of the MET gene polymorphism on immune cell activity as well as further examine the impact of environmental toxins (including ethyl mercury) on the gene expression-dependent function of maternal immune cells.

Epidemiological research on autism in Jamaica (Federally Funded, NIH)

The prevalence of autism spectrum disorders (ASD) appears to be on the rise in developed countries and has become a serious public health concern. In most developing countries, however, the nature and prevalence of factors associated with ASDs are unknown. The long term goal of this planning project is to develop capacity for conducting large scale population-based ASD studies in Jamaica. First, the diagnostic criteria used in Jamaica and the United States will be compared. Then, questionnaires regarding the demographic and socioeconomic position, occupation, and drinking habits of each child’s parents will be used, and information will be gathered about family history of developmental disorders, family size, birth order of the affected child, and whether the child is taking any medications. An age and sex matched case-control study, including a dietary questionnaire, will also be conducted to investigate whether environmental exposures to mercury, lead, arsenic, and cadmium play a role in autism. Blood and saliva samples will be collected to determine if any DNA polymorphisms that might affect interactions with heavy metals are present in children with ASD. New knowledge of potential environmental risk factors for ASD may arise from this research, thereby reducing physical, psychological, and economic burdens on the child, family, and society and helping parents make decisions about avoiding exposure to environmental contaminants.

An investigation on the potential harmful effects of mercury in the nonhuman primate (Funded by SafeMinds)

An investigation into the effect of mercury on neurons, astrocytes, and microglia on the central nervous system of the nonhuman primate.

Investigating the effect of mercury on ASD, AD and ASD regression (Funded by SafeMinds)

An investigation into the influences of demographics and environmental variables in the development of neurodevelopmental problems such as AD, ASD, and ASD-regression

The effect of mercury and neuropeptide triggers on human mast cell release of neurotoxic molecules (Funded by SafeMinds)

An investigation to determine the pro-inflammatory effects of mitochondrial DNA with and without mast cell triggers.

Does mercury and neurotension induce mitochondrial DNA release from human mast cells and contribute to auto-immunity in ASD? (Funded by SafeMinds)

Further investigation into preliminary data that neurotensin (NT) stimulates mast cell activation and that NT is elevated in young children with autism spectrum disorder.

Toxicant-induced autism and mitochondrial modulation of nuclear gene expression (Federally Funded: DoD)

Autism has been associated with epigenetic changes: Tiny chemical tags in the regulatory regions of genes that affect how genes express themselves by turning them on or off. One gene often decreased in expression in the brain tissue of autistic individuals is MECP2, a gene that governs the expression of genes crucial to brain development. Exposure to environmental pollutants is also thought to play a role in autism. These two phenomena both involve a small cellular organ called mitochondria. The suspect environmental pollutants are toxic to mitochondria, which play a critical role in epigenetics: Pollution exposure can lower the amount of mitochondrial DNA (mtDNA) in a cell, causing an increase in placement of epigenetic tags by DNMT1 that leads to gene silencing. We hypothesize that exposure during pregnancy to pollutants toxic to mitochondria causes a decrease in mtDNA copy number and increased placement of epigenetic tags by DNMT1 on key developmental genes, affecting pathways that have direct roles in the development of autism. We will expose mice, during pregnancy, to selected toxicants and evaluate adult behavior and associated biochemical changes in brain tissue. Valproic acid will be used as a positive control, with saline as a negative control. The environmental pollutants lead, arsenic, cadmium, manganese, mercury, and permethrin will be investigated for their potential to induce autistic behavior changes. Brain tissue will then be used for molecular studies of mtDNA copy number, expression of DNMT1, and alterations to the epigenome on both a genomewide and gene-specific level.


By Matt Carey

Note: I serve as a public member to the IACC. My views here and elsewhere are my own, not those of the Committee.

No, the autism prevalence in Denmark did not go down with the removal of thimerosal (again!)

17 Jul

There’s a story that goes around the vaccine/autism groups that, contrary to published reports, the autism rate in Denmark went down after thimerosal was removed from their vaccines. Of course, this is all part of a cover-up. I discussed this previously in No, the autism prevalence in Denmark did not go down with the removal of thimerosal. In that piece, I looked at a number of published studies and found that the autism rate in Denmark has continued to climb post thimerosal. Later, a study came out which in one place listed autism prevalence vs year for Denmark, and I discussed that as Autism, Denmark and again no link with vaccines.

Denmark removed thimerosal from pediatric vaccines in 1992. One of the graphs I created from the published data is here:

See how the prevalence of childhood autism (autistic disorder, dark purple bars) is higher for all birth years post 1992? ASD prevalence (lighter bars) is more complex–it peaks. ASD prevalence is higher for most years after 1992, but there is that peak. At the time I speculated that someone would rework these data and claim “see! there was a drop! Vaccines cause autism!”. It would be very dishonest and misleading, so I’m not surprised to see that the Age of Autism blog did exactly that.. Let me take a second to discuss how this is dishonest. First, the prevalence of childhood autism is always higher post 1992. This is what the Age of Autism and similar sites consider “real autism”, but they just ignore that. Even one of their own commenters asked about this and was ignored. Next, even with the apparent peak in ASD prevalence, the prevalence is higher for kids borh after 1992. If thimerosal was the primary cause of autism (or even a large cause), the prevalence should have dropped immediately after 1992 in both the childhood autism and ASD groups. It didn’t.

Why is there a peak in the ASD prevalence? Most likely years of follow up. Kids with, say, Asperger syndrome are diagnosed later. The data in the graph above were for kids diagnosed by 2010. So the kids in birth year 2004 were only 6 when the study was performed and fewer of them were diagnosed by the time the study was performed.

At age 6, many autistics remain undiagnosed. If you are skeptical that kids are diagnosed late, read on.

Another study has been recently published on autism prevalence in Denmark, The increasing prevalence of reported diagnoses of childhood psychiatric disorders: a descriptive multinational comparison. In this study they compared autism prevalence as well as ADD, Tourette syndrome and OCD in 3 different countries and noted that the trends were similar. The Simons Foundation SFARI blog has covered this in Autism not the only neurodevelopmental disorder on the rise.

Thimerosal was removed in Denmark in 1992. The autism prevalence increased after that. Same for Sweden. I’m not sure when Finland phased out thimerosal, but I suspect it’s about the same time. In which case, again, the rise in prevalence following the removal works against the thimerosal hypothesis.

This all said, what caught my eye was the supplemental material available with the paper. They show autism prevalence for various birth cohorts by age. For example, for kids born in 1990-1992, the authors give the autism prevalence at age 5, 8, 10, 15 and 20.

But, you say, it’s autism prevalence, how can it change with age? Autism is obvious and once the DSM IV was published, everyone has the exact same idea of who is autistic, right? Let’s use these data to see. Autism prevalence is almost always the prevalence of identified autism. Which is to say, it’s a count of who has a diagnosis already. If someone isn’t diagnosed, s/he isn’t counted in these sorts of prevalence reports. So, we can test the idea that (a) autism is obvious and (b) the understanding of what autism is doesn’t change.

So let’s look at data for Danes born in 1990-92. Autism prevalence vs age. If autism is obvious and the definition isn’t changing, this should be a level line. Or, let’s say, after an initial increase as kids are diagnosed, this will be a flat line. Right? Oh, you know with this much of a lead in, this isn’t going to be the case.

denmark1

The line is not just a guide to the eye. It’s a fit. For some reason, these data are almost a straight line. Autism prevalence increased as the kids aged.

edit to add: in case you prefer bar graphs I’ve added one (for both, click to enlarge).

denmark2

Consider just the last two points: age 15 and age 20. Autism prevalence went from 73.4 to 109.7 per 10,000. That’s like a 50% increase in 5 years! Is that an epidemic? No. Those autistics were always there. Just uncounted. And they were 15 years old. They were missed.

There are a few ways to look at the increase in autism prevalence in Denmark, the US and elsewhere:

1) The rates reported are accurate counts of how much of our population is autistic and, thus, represent a real increase.
2) There are social influences like shifts in our understanding of what is autism and how well we can diagnose autism and these are behind the increase.
3) Much of the increase is socially driven. It could be all. We can’t rule out that some is a real increase.

It’s not hard to see that (3) fits the data.

People pushing the idea of an autism epidemic don’t even accept that social factors and “real” increases are on the same footing. No, they promote the idea that social influences are a “denial” mechanism. But the fact is, there are data showing that social influences have had a huge impact on autism prevalence. The only data pointing to a “real” increase are those linking increased risk of older parents with increasing age of parents to the autism prevalence (estimated to account for 4-10% of the observed increase in California). This is both a “real” increase and a socially driven increase, by the way.

For what it’s worth, “real” isn’t in “scare quotes”. Some people use “real” to mean “a secular increase in autism prevalence. An actual increase in the fraction of autistics born.” Social factors are real, making real changes in autism prevalence.

Lastly, people will say, “autism is a crisis! If you don’t acknowledge the epidemic you aren’t taking this seriously!” Crisis: a difficult or dangerous situation that needs serious attention. Crisis does not equate to epidemic.

The fact that autistics are being missed *is* a crisis. It is something I take seriously and feel “needs serious attention”. Also, the idea that there could be an increase in autism prevalence is a very serious question getting very serious attention.

Are those promoting the “vaccine epidemic” idea actually treating autism as a crisis? No, they are not. Avoiding the question of undiagnosed autistics is denialism and is hurting our communities.

I know this article is pounding nails into a coffin that is already not only nailed shut, but arc-welded shut and then encased in concrete. Beyond that, the acceptance for the thimerosal causation idea–which was never a majority idea among parents– has waned, dramatically. New parents know their kids were not exposed to thimerosal. That, more than anything, killed the hypothesis within the autism parent community. Parents aren’t chelating their kids any more. The idea is dead. Sure there’s a hard core of believers still talking about it. And, more, they use this idea to scare others about vaccines.

Why talk about it then? For those few people who do get suck into the autism-as-mercury-poisoning world today. It’s still a very damaging notion, leading parents to lead lives of guilt and to become a ready market for the faux-therapies that have been built around the thimerosal idea. They need to know–the idea has no merit, whatsoever. The data are as clear as data can get. Thimerosal in vaccines doesn’t cause autism.


By Matt Carey

No, autism is not caused by lyme disease

16 Jul

In what is one of the shortest abstracts I’ve seen, a group from NIH reports on Lack of serum antibodies against Borrelia burgdorferi in children with autism.

Straightforward experiment: test the blood from autistic kids, developmentally delayed kids and “healthy controls”. Check if the blood samples have antibodies for the bacterium that causes lyme disease. Autistic kids have the same level of antibodies as do other kids. Below the threshold for lyme disease. I.e. there is no evidence for an association between Lyme disease and autism.

here’s the abstract:

It has been proposed that Borrelia burgdorferi infection is present in ∼25% of children with autism spectrum disorders. In this study, antibodies against Borrelia burgdorferi were assessed in autistic (n = 104), developmentally delayed (n = 24), and healthy control (n = 55) children. No seropositivity against Borrelia burgdorferi was detected in the children with and without autism. There was no evidence of an association between Lyme disease and autism.

I think the groups who believe in a link are small. But the idea persists, complete with treatments that at best are doing nothing and at worst are causing harm.


By Matt Carey

Why won’t the government fund vaccine/autism research?

15 Jul

This question gets brought up a lot by some parent advocates. The are informed by groups promoting the idea of vaccine causation that the government is blocking this work. The evidence points strongly away from vaccines as a primary cause of autism, and investment in this area doesn’t seem wise. At least that’s the viewpoint of the majority of parents (including myself), autistics and researchers. But some remain unconvinced and want vaccine/autism research performed. And they are upset that none of this work is being performed.

Here’s a different question: why are the groups who promote the idea that vaccines cause autism failing to inform their members that, yes, indeed vaccine/autism research is being performed?

Or, to put it simply: vaccine/autism research is being performed and it’s being funded by the government. But you wouldn’t know that if you read, say, the Age of Autism blog, Generation Rescue’s website, SafeMinds’ website, or the other groups advocating for this research. If you are interested in vaccine/autism research and you are reading about these projects for the first time here, ask yourself “why have these orgs not informed me of this?”.

As noted here recently, Tom Insel discussed an upcoming vaccine/autism study. Already commissioned, performed and in the publication stage. That announcement was in April. What was the response from the community that has pleaded for vaccine/autism research? For the first few months: Silence. In July, SafeMinds finally put out an article showing that they were “worried” about this study. I don’t see much discussion of this announcement from other groups or outlets.

I’m not surprised by this. I’ve noted before that work on areas such as vaccines, mercury, environmental risk factor research and GI dysfunction don’t get discussed by the groups that are focused on these topics. I’ve covered the research in these areas more than they have.

So let’s get back to what other work is going on in vaccines and autism. Let’s start with the simple question: how would you find out? One place is the IACC/OARC Autism Spectrum Disorder Research Portfolio Analysis Web Tool. That could use updating, but it is an easily searchable database. Another place is NIH Reporter. It’s less easy to use than the Portfolio Analysis Tool and includes all of NIH. I.e. it covers non autism topics and doesn’t include projects being done outside of NIH (say, by Autism Speaks or other private funders). But, search Reporter for autism and vaccines or mercury and what do you get? Quite a number hits. Let’s consider a few.

How about:

There’s a study by Ian Lipkin’s group at Columbia titled: GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

There’s a study by Gene Sackett’s group, A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES. This appears to be a follow on project to the Laura Hewitson studies that were discussed a great deal online a few years ago.

Isaac Pessah’s group at the UC Davis MIND Institute has a project NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM. Prof. Pessah also had a multiyear project ENVIROMENTAL FACTORS IN THE ETIOLOGY OF AUTISM

Judy Van de Water’s group at UC Davis MIND Institute has a project IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.

The Lewin Group study (which I believe is the one mentioned by Tom Insel) STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES. (Just a note–see how this has been publicly available information for a year?)

There’s the CHARGE study, which is looking at a large array of potential environmental risk factors, including specifically mentioning mercury. THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Here’s a 2014 grant to Ray Palmer, well known to the groups promoting mercury as a cause of autism, PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN.

The EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA – PHASE II project is continuing (hence the Phase II) and includes work on mercury.

There are more projects. Some I left out because they are older. But I think the point is made and is very clear: vaccine/autism and mercury/autism research are being funded.

And that is without even discussing how research on the biology of autism feeds into all etiological questions. Whether it’s vaccine, genetics or what have you, if you understand the biology, you have a better chance of understanding the cause. (when I searched NIH Reporter with the terms Autism and Immune, I got 25 pages of hits. Sure, not all are on-topic, but that’s 25 pages, 606 topics).

Here are the full abstracts–with emphasis added by me–for the NIH Reporter projects mentioned above.

GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT.

Abstract Text:
Reports of increasing prevalence of autism spectrum disorders (ASDs), a set of highly genetic conditions, are intensifying interest in the role of environmental exposures, including infectious, immune, and toxic factors. Retrospective studies exploring associations between environmental factors and ASDs are compromised by selection bias, small sample sizes, possibly invalid diagnosis, and absence of biologic measures. This prospective study will employ an unselected birth cohort of 75,500 in which cases are ascertained through screening of the entire population, diagnoses established using uniform procedures, extensive histories and clinical data obtained, and biologic samples collected serially throughout pregnancy and early childhood. The application of high throughput laboratory assays to derive maximal information from developmentally-influenced, finite, and nonrenewable biologic samples, and inclusion of early screening and diagnostic assessments, will permit an unprecedented, rich view of the longitudinal trajectory and nascent signs and symptoms of ASDs, facilitate discovery of biomarkers, and afford unique insights into the role of gene:environment interactions in ASD pathogenesis. Specific aims are to: (1) establish the autism Birth Cohort (ABC) through ascertainment of cases of autism spectrum disorder (ASD, N=150-233) and selection of controls (N-1000) from the Norway Mothers and Child (MoBa) cohort; (2) examine biologic pathways that may predispose to ASD, through evaluation of immune, endocrine, and neuroregulatory factors in mothers during early gestation or at birth and in children, at birth or 30 months postnatal; (3) identify environmental factors that may be directly or indirectly associated with ASD, including pre- or postnatal infection, vaccination, very low birth weight or other obstetric risk factors in which infections are implicated, dietary and/or environmental exposure to methylmercury; (4) describe the natural history of clinical, anthropometric, and neurobehavioral features of ASD; and (5) explore genotypic influences that may be directly or indirectly associated with ASD by testing associations of ASD and/or its endophenotypes with family history of autoimmune disease or selected candidate genes, and investigating conditional gene-environment effects using antecedent factors found to influence ASD risk.

NIH Spending Category:
autism; Brain Disorders; Clinical Research; Genetics; Immunization; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric; Prevention; vaccine Related

Project Terms:
autism spectrum disorder; Autistic Disorder; Autoimmune Diseases; base; Biological Assay; Biological Markers; Birth; Candidate Disease Gene; case control; Child; Clinical; Clinical Data; cohort; Cohort Studies; Collaborations; Collection; Confusion; Control Groups; design; Development; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; disorder risk; Drops; early childhood; Endocrine; endophenotype; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Evaluation; Exposure to; Family history of; gene environment interaction; Genes; Genetic; Hereditary Disease; Immune; immune function; Infection; insight; interest; Investigation; Laboratories; Life; Measles; Measures; member; Mercury; Methylmercury Compounds; Mothers; Mumps; Natural History; Nested Case-Control Study; neurobehavioral; Neurodevelopmental Disorder; Norway; novel; Pathogenesis; Pathway interactions; Phase; Population; postnatal; Pregnancy; prenatal; Prevalence; Procedures; prospective; Prospective Studies; Recording of previous events; Relative (related person); Reporting; Research; Research Design; Retrospective Studies; Risk Factors; Role; Rubella; Sample Size; Sampling; Screening procedure; Selection Bias; Signs and Symptoms; Specimen; Testing; Vaccination; Vaccines; Vacuum; Very Low Birth Weight Infant

A PRIMATE MODEL OF GUT, IMMUNE, AND CNS RESPONSE TO CHILDHOOD VACCINES.

Abstract Text:
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject’s principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diagnoses of childhood developmental disorders involving autism-spectrum symptoms are increasing, estimated to affect 1 in 100 children in the United States. Childhood Vaccines have been hypothesized to be contributory factors to this increase. The childhood vaccine regimen has an experimentally unstudied potential for cumulative and synergistic toxicities and possible immunologic interference to normal development. A prior study developed a primate model to assess neurodevelopmental consequences of the 1994-1999 pediatric thimerosal vaccine regimen (1994-1999). Significant neurodevelopmental deficits were evident for vaccinated animals in survival reflexes and standardized cognitive tests, and exposed animals developed gastrointestinal inflammation associated with focal transmural colitis, lymphoid hyperplasia, and syncytia.

NIH Spending Category:
autism; Brain Disorders; Cancer; Digestive Diseases; Immunization; Lymphoma; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric; Rare Diseases; vaccine Related

Project Terms:
Affect; Animals; Autistic Disorder; Child; Childhood; Cognitive; Colitis; cost; Development; developmental disease/disorder; Diagnosis; Funding; gastrointestinal; Giant Cells; Grant; Immune; Immunologics; Inflammation; lymphoid hyperplasia; Modeling; National Center for Research Resources; Neurodevelopmental Deficit; Primates; Principal Investigator; Reflex action; Regimen; Research; Research Infrastructure; Resources; response; Source; Symptoms; Testing; Thimerosal; Toxic effect; United States; United States National Institutes of Health; Vaccinated; Vaccines

NEURODEVELOPMENTAL TOXICOLOGY OF AUTISM

Abstract Text:
The long range goal is to determine if exposure to environmental toxicants early in development contributes to the etiology of neurodevelopmental disorders such as autism. A related goal is to determine whether susceptibility to autoimmune disease increases the neurotoxicity of environmental contaminants and increases the risk for developing disorders such as autism. Understanding how exposure to environmental toxicants may contribute to the etiology of neurodevelopmental disorders is important so that the exposure risks can be identified and minimized. If immune system dysfunction is found to increase the risk of exposure to environmental toxicants, then exposure limits to toxic substances can be lowered, and children with immune system dysfunction who may be at increase risk can be identified and protected. The specific aims are to expose mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity perinatally to either methylmercury (MeHg), polychlorinated biphenyl 95 (PCB 95) or polybrominated diphenyl ether 47 (BDE 47). We will then compare the effects of toxicant exposure between these mouse strains on brain development, complex social behaviors, and immune system function. The hypothesis is that perinatal exposure to each of these toxic substances will impair brain development and behavior, and that suscepbility to autoimmune disease will increase the neuro- and immunotoxicity of these agents. We will also explore a potentially new model of autism in mice injected prenatally with unique autoantibodies isolated from the serum of mothers who have given birth to two more more autistic children. Brain development will be examined histologically using stereological procedures and immunohistochemistry. Complex social behaviors will be studied using behavioral testing procedures established in our laboratory that measure social recognition, social interaction and social communication in mice. Immune system status will be established by measuring cytokines, chemokines, immunoglobulins, and quantifying immune system response to antigenic stimulation. In addition, seizure susceptibility will be measured in toxicant-exposed mice as well as measures of synaptic excitibility and plasticity in hippocampal brain slices. These studies will provide critical new information on the role of the immune system and its interaction with environmental contaminants in autism and other neurodevelopmental disorders.

NIH Spending Category:
autism; Autoimmune Disease; Behavioral and Social Science; Brain Disorders; Epilepsy; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurodegenerative; Neurosciences; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period

Project Terms:
Age; Animal Testing; Antibodies; Anxiety; autistic Children; Autistic Disorder; Autoantibodies; Autoimmune Diseases; Autoimmune Process; Autoimmunity; Behavior; behavior test; Behavioral; Biological Assay; Birth; Brain; CCL2 gene; CCL3 gene; CCL4 gene; Cerebellum; chemokine; Chemokine (C-C Motif) Ligand 4; Child; Complex; cytokine; density; Development; developmental disease/disorder; developmental neurotoxicity; Disease; Environmental Pollution; Enzyme-Linked Immunosorbent Assay; Etiology; Exposure to; fetal; Fibroblast Growth Factor; Flurothyl; Fright; Glutamate Receptor; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Hippocampus (Brain); Histologic; Homer 1; human TNF protein; IL8 gene; Immune response; Immune system; Immune System and Related Disorders; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Immunohistochemistry; Immunophilins; immunotoxicity; In Vitro; in vivo; Infection; Interferon Type II; Interleukin-10; Interleukin-17; Interleukin-4; Interleukin-5; Interleukin-6; Kindling (Neurology); Laboratories; Learning; Leptin; link protein; Long-Term Potentiation; Measures; Memory; Metabotropic Glutamate Receptors; Methods; Methylmercury Compounds; Mitogens; Modeling; Mothers; mouse model; Mouse Strains; Mus; N-Methylaspartate; neurobehavioral disorder; neurodevelopment; Neurodevelopmental Disorder; Neurologic; Neuronal Injury; Neurons; neurotoxicity; offspring; Pentylenetetrazole; Perinatal; Perinatal Exposure; phenyl ether; Plasma; Poisons; Polychlorinated Biphenyls; postnatal; Predisposition; pregnant; prenatal; prenatal exposure; Preparation; Principal Investigator; Procedures; programs; Proteins; RANTES; receptor; receptor function; repaired; Research Design; Research Personnel; research study; response; Risk; Role; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Seizures; sensory gating; Sensory Motor Performances; Serological; Serum; Signal Pathway; Signal Transduction; SJL Mouse; SJL/J Mouse; Slice; Small Inducible Cytokine A3; social; Social Behavior; social communication; Social Interaction; Source; Splenocyte; Structure; Synapses; synaptotagmin; System; T-Cell Proliferation; Testing; Tetanus; Tetanus Toxoid; Tetanus vaccine; Toxic Environmental Substances; toxicant; Toxicant exposure; Toxicology; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factors; Western Blotting; Work; Xenobiotics

IMMUNOLOGICAL SUSCEPTIBILITY OF AUTISM.
Abstract Text:
Recent studies indicate that immune function in children with autism spectrum disorder (ASD) is profoundly altered compared to developmentally healthy controls. There is a strong interface between the immune system and the neurologic network, and successful neurodevelopment is contingent upon a successful interaction between these two systems. We have identified several aspects of immune dysfunction in patients with autism compared with typically developing controls. These include a reduced response to vaccine antigens of bacterial origin, altered cytokine levels in plasma and upon stimulation of PBMC, increased levels of leptin in patients with early onset autism, and autoantibodies to brain antigens. This wide and complex variety of immune anomalies noted in our first funding period is in keeping with the broad range of phenotypes encompassed by the autism spectrum. Thus, we will build upon our earlier findings of both serologic and cellular changes in immune function. While our studies in the previous project period were aimed at a broad analysis of immune function in patients with autism, the current proposal will address the mechanisms responsible for the numerous alterations in immune homeostasis uncovered in our earlier studies. Therefore, our primary focus will be on the mechanisms responsible for such anomalies in immune function through an in depth analysis of cellular immune function. Our overall hypothesis is that patients with autism have a fundamental defect at the cellular level that ultimately leads to abnormalities in immune function and heightened susceptibility to environmental triggers. To examine this, we propose to: (1) examine longitudinally the serologic profile of children with ASD to ascertain whether the various immune changes noted in our first studies are maintained and/or deteriorating further; (2) determine which immune cell population(s) plays a critical role in the immune dysfunction seen in patients with autism; and (3) fully characterize the autoantibody response in a subpopulation of children with ASD and some mothers of children with ASD. It must be noted that due to the highly heterogeneous nature of autism, there will potentially be immunologic differences that relate to sub-groups of patients with autism. Therefore, we will carefully define the study groups based on our current data to include children with early onset autism, children with delayed onset/regressive autism, general population controls, and children with developmental disorders without ASD. The studies will be performed on CHARGE subjects formerly analyzed by our laboratory (CHARGE-BACK study). This will allow us to extend our prior studies longitudinally to determine if the immune dysregulation, such as increased leptin levels in the early onset patients, remains over time. The following aims address both the serologic and cellular aspects of immune function in patients with autism.

NIH Spending Category:
autism; Brain Disorders; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Neurosciences; Pediatric

Project Terms:
Address; Age; anti-IgM; Antibodies; Antigens; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; B-Lymphocytes; Back; base; Behavior; Blood Cells; Brain; calcium indicator; Calcium Signaling; Cell Culture Techniques; Cell physiology; Cell Proliferation; Cell surface; Cells; Child; Color; Complex; Cultured Cells; cytokine; Data; Defect; Development; developmental disease/disorder; Digestion; Disease; Dose; Dyes; early onset; Environmental Health; Etiology; fetal; Flow Cytometry; Flu virus; Frequencies (time pattern); Funding; Gel; General Population; HLA-DR Antigens; Homeostasis; Human; IgE; Immune; immune function; Immune system; Immune System Diseases; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologics; Label; Laboratories; Lasers; Leptin; Maps; Mercury; Microarray Analysis; Mitogens; Modeling; Mothers; Mus; Nature; neurodevelopment; Neurologic; Oligonucleotides; Pathogenesis; Pathology; Patients; Pattern; Peptides; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Play; Poly I-C; Population; Population Control; Predisposition; Pregnancy; Principal Investigator; Production; programs; Reagent; research study; response; RNA; Role; Serological; Serum; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staining method; Stains; System; T-Lymphocyte; Testing; Time; TNFSF5 gene; Tube; Up-Regulation (Physiology); Upper arm; vaccine Antigen; Xenobiotics

STUDY OF HEALTH OUTCOMES IN CHILDREN WITH AUTISM AND THEIR FAMILIES

Abstract Text:
This contract modification is to extend and supplement Contract HHSN271201000033C, consistent with the scope of work of “Study of Health Outcomes in Children with autism and Their Families¿ in order to access the currently validated database developed under the contract to provide for further analysis . Autism Spectrum Disorder (ASD) is a significant public health concern, with an estimated prevalence of 1 in 88 children in the United States. Much of the research to date has focused on the core social and communication deficits of ASD, but there are anecdotes and some survey data suggesting that the rate of comorbid health conditions may also be elevated in this population. Furthermore, despite several large-scale epidemiological studies that have assessed but not found any potential association between ASD and vaccinations, public concerns persist about such a causal link. At least partly as a consequence, health officials in the United States have reported an increased rate of vaccine refusal in the general population. The Study of Health Outcomes in Children with autism and their Families was begun two years ago. Under this contract, the Contractor analyzed a large dataset of retrospective commercial health plan claims of 46,236 children with ASD, their parents and siblings, and a comparison cohort of children and family members. They successfully completed the analyses requested in the original statement of work, which included a study of the validity of ASD diagnoses in the claims data, and descriptions of health outcomes and health care utilization of the ASD cohort, their family members, and the comparison cohorts.

NIH Spending Category:
autism; Brain Disorders; Immunization; Intellectual and Developmental Disabilities (IDD); Mental Health; Pediatric; Prevention; vaccine Related

Project Terms:
Anecdotes; autism spectrum disorder; Autistic Disorder; Child; cohort; Contractor; Contracts; Data; Data Set; Databases; Diagnosis; Epidemiologic Studies; Family; Family member; General Population; Health; health care service utilization; Health Planning; Link; Modification; Outcome; Parents; Population; Prevalence; public health medicine (field); Recording of previous events; Reporting; Research; Siblings; social communication; Surveys; United States; Vaccination; Vaccines; Work

CORE D: MOLECULAR GENOMICS CORE

Core 4 is the Molecular Core. It serves as the central resource for the projects that isolate and process RNA on Affymetrix microarrays, and for performing RT-PCR confirmation of the microarray data for those projects. The UCD Affymetrix Core Facility is run by Dr. Jeffrey Gregg and is equipped with fluidics stations, hybridization ovens, and the new scanner required to scan the human Affymetrix U133 2.0PLUS arrays. Preliminary data from the previous CHARGE study has shown that there are changes in gene expression in the blood of children with autism compared to control children in the general population (GP) and to control children with mental retardation and developmental delay (MR/DD). The blood genomic profile in children with autism without regression (A) was different from controls, autism spectrum disorder (ASD) and different from children with autism with regression (A-R). In addition, there is a group of regulated genes in most children with A, A-R and with ASD that are expressed by natural killer (NK) cells in peripheral blood, suggesting an abnormality in this cell type that is common to all types of autism. These NK-cell related genes are expressed by all of the autism phenotypes including A, A-R and ASD, and hence may point to common pathways that underlie the common language and behavioral abnormalities in all three disorders. This core will be utilized by the projects as follows. Project #1: Aim #1: Perform genomic (RNA expression on microarrays) studies on blood from children with autism in the 4-9 year old range, and compare to the blood genomic profiles we have obtained in children with autism in the 2-5 year old age range. Aim #2. Compare gene expression as a function of blood metal levels in both age groups in A, A-R, ASD, MR/DD and GP groups. Aim #3. Examine genomic profiles in pregnant mothers who have previously given birth to an autistic child to determine if there is a specific genomic profile that correlates with whether the mother’s fetus is destined to develop autism. Project #2. Aim #1. Describe the gene expression profiles in the blood using specific white blood cell subsets including NK cells for children with autism without regression, autism with regression, and ASD children compared to GP and delayed children. Aim #2. Examine gene expression following stimulation or activation of specific white blood cell subsets of A, A-R, ASD, MR/DD and GP children with: low level mercury; immune cell stimulation/activation with vaccine antigens and cell-specific mitogens; and xenobiotics. Project #3. Compare gene expression profiles in the blood of children with autism to the blood of experimental animals exposed to toxicants including organic mercury, PCB 95, and PBDE 47 (Project #3).

NIH Spending Category:
autism; Biotechnology; Brain Disorders; Genetics; Mental Health; Mental Retardation (Intellectual and Developmental Disabilities (IDD)); Pediatric

Project Terms:
5 year old; 9 year old; Accounting; Age; age group; Animals; autism spectrum disorder; autistic Children; Autistic Disorder; Autoantibodies; base; Behavioral; Birth; Blood; Blood specimen; cell type; Cells; chemokine; Child; Core Facility; cytokine; Data; Developmental Delay Disorders; Disease; Environmental Health; Fetus; Gene Expression; General Population; Genes; Genetic; Genetic Transcription; Genome; Genomics; Human; Immune; immune function; Inherited; Language; Leukocytes; Mental Retardation; Mentally Disabled Persons; Mercury; Metals; Mitogens; Molecular; Molecular Profiling; Mothers; Natural Killer Cells; Pathway interactions; Patients; pentabromodiphenyl ether; peripheral blood; Phenotype; Polychlorinated Biphenyls; Population Group; pregnant; Principal Investigator; Process; programs; Resources; Reverse Transcriptase Polymerase Chain Reaction; RNA Processing; Running; Scanning; Subgroup; Surveys; Toxic Environmental Substances; toxicant; vaccine Antigen; Xenobiotics

THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT

Abstract Text:
DESCRIPTION (provided by applicant): Few rigorous epidemiologic studies have addressed the environmental causes and biologic underpinnings of autism spectrum disorder (ASD). The CHARGE (Childhood autism Risks from Genetics and Environment) Study is a large, population-based case-control investigation of environmental risk factors, broadly defined, in relation to ASD and developmental delay without ASD symptoms, with referents from the general population. Fieldwork began in 2003, and by now CHARGE has published widely on exposures such as air pollution, mercury, flame retardants, maternal nutritional status in the peri-conception, untreated fever during pregnancy, mitochondrial dysfunction, candidate genes, a wide array of functional immune markers in both the child and the mother, and maternal metabolic conditions including obesity and diabetes. This last finding is notable, given the epidemic of obesity and type 2 diabetes that has occurred in parallel with the steady rise in ASD over the last few decades. Moreover, an emerging literature implicates several endocrine disrupting chemicals as contributing to obesity and metabolic dysregulation, including hyperinsulinemia, and to neurodevelopmental disorders as well. This project therefore builds upon these observations in several ways. First, obesity and type 2 or gestational diabetes will be examined in a larger sample, and glucose challenge test (GCT) results for the first time, to determine associations not only with development of ASD and intellectual impairment in the children, but also with specific speech and language delays, behavioral phenotypes such as attention deficits or hyperactivity, and gene expression. Second, these maternal metabolic conditions will be evaluated for associations with markers of both metabolic and immune dysregulation to be measured in neonatal bloodspots. Third, the predictive value of neonatal bloodspot markers for a later diagnosis of ASD or other child developmental and behavioral outcomes will be assessed. Fourth, the maternal metabolic conditions will be analyzed for potential links with upstream exposures to phthalates and anti- bacterial compounds, ubiquitous chemicals in common household products. Finally, this project will examine how gene variants that play a role in biochemical pathways relevant to the processes under study may influence susceptibility of the mother, the neonate or the child. To ensure adequate power for this analysis of gene-environment interaction, the sample size will be increased to 2400 children. This project addresses several goals set by the NIH Interagency autism Coordinating Committee: 1) to discover environmental factors contributing to ASD, particularly in the prenatal period, 2) to understand biological mechanisms for ASD risk, including gene-by-environment interactions, and 3) to identify children at risk for ASD at earlier time points. Results of this detailed inquir into early exposures, maternal pathophysiology and prognostic markers in the newborn will set the stage for developing prevention strategies.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: This project addresses several issues of direct public health relevance, and the science to be produced will lead to benefits in a wide cross-section of the U.S. population. Because obesity is reaching epidemic proportions and other metabolic conditions such as Type 2 diabetes, gestational diabetes, and dyslipidemia are rising steeply, understanding environmental causes has tremendous public health potential for moving us closer to effective prevention strategies. If environmental chemicals used in common household products do prove to adversely affect body weight, measures can be taken to either reformulate those products, removing them from the market, or to educate consumers on how to avoid them. Similarly, steady increases in ASD might be curbed if the postulated causal pathway is supported by the evidence.

NIH Spending Category:
autism; Behavioral and Social Science; Brain Disorders; Clinical Research; Diabetes; Genetic Testing; Genetics; Intellectual and Developmental Disabilities (IDD); Mental Health; Neurosciences; Nutrition; Obesity; Pediatric; Perinatal Period – Conditions Originating in Perinatal Period; Prevention

Project Terms:
Address; Affect; Age; aged; Air Pollution; Anti-Bacterial Agents; Attention; autism spectrum disorder; Autistic Disorder; Behavior; Behavioral; Biochemical Pathway; Biological; Biological Markers; blood glucose regulation; Body Weights and Measures; C-Peptide; Candidate Disease Gene; case control; CCL2 gene; chemical association; Chemicals; Child; Childhood; Conceptions; cytokine; Data; Development; Developmental Delay Disorders; Diabetes Mellitus; Diagnosis; disorder risk; Dyslipidemias; Endocrine Disruptors; Ensure; Environment; environmental chemical; Environmental Risk Factor; Epidemic; Epidemiologic Studies; ESR1 gene; Exposure to; Fever; Flame Retardants; Functional disorder; gene environment interaction; Gene Expression; General Population; Genes; Genetic Risk; Gestational Diabetes; Glucose; glucose metabolism; Goals; high risk; Household; Household Products; human TNF protein; Hyperactive behavior; Hyperinsulinism; Hypertension induced by pregnancy; Immune; immune function; Immunologic Markers; Impairment; inattention; Inflammation; Inflammatory; Insulin Resistance; insulin sensitivity; interest; Interleukin-6; Investigation; Language Delays; Lead; Leptin; Link; Literature; Marketing; Maternal Exposure; Measures; mercury; Metabolic; Metabolic Marker; Metabolism; mitochondrial dysfunction; Mothers; Neonatal; neonate; neurodevelopment; Neurodevelopmental Disorder; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Nutritional status; Obesity; Outcome; Pathway interactions; Phenotype; phthalates; Play; Population; population based; PPARG gene; Predictive Value; Predisposition; Pregnancy; prenatal; Prevention strategy; Process; prognostic; Prognostic Marker; public health medicine (field); public health relevance; Publishing; Regulation; Risk; Role; RORA gene; RPL10 gene; Sample Size; Sampling; Science; Self Care; Speech Delay; Staging; Symptoms; Test Result; Time; Triclosan; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Variant; Variation (Genetics)

PRENATAL TIMING OF HEAVY METAL EXPOSURES FROM AUTISTIC AND NON-AUTISTIC CHILDREN

DESCRIPTION (provided by applicant): Little is known about the etiology or risk factors for autism, a disease affecting 1 in 50 children in the U.S. While genetic and environmental factors are thought to act together, the specific mechanisms are not known and the measurement of environmental risk factors during critical periods of neurodevelopment has been lacking. This case-control study seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD. Using the proposed biomarker, we will directly assess fetal exposure, and will not rely on maternal biomarkers which may only provide an indirect measure of fetal exposure to metals. This work will have substantial impact on epidemiologic investigations of the relation of early life chemical exposures to ASD and other neurodevelopmental disorders as it can be used to objectively reconstruct both exposure intensity and timing.

Public Health Relevance Statement:
PUBLIC HEALTH RELEVANCE: Little is known about the causes of autism. This proposal seeks to apply a novel dental biomarker of early life metal exposure, including in utero, to identify risk factors for ASD. Beyond looking at exposure intensity, our application is novel in that we will be able to identify differences in exposure timing between cases and controls. This will allow us to identify critical windows when exposure, even at low levels, increases the risk of ASD.

Project Terms:
Accounting; Address; Affect; Aluminum; analytical method; Animals; Apatites; Arsenic; autism spectrum disorder; autistic Children; Autistic Disorder; Binding (Molecular Function); Biological; Biological Markers; bone; Cadmium; Calcified; Calcium; case control; Case-Control Studies; Chemical Exposure; Chemicals; Child; Childhood; Chromium; critical period; Data; deciduous tooth; Dental; Dentin; Development; Disease; early life exposure; Elements; Environment; Environmental Exposure; Environmental Risk Factor; Epidemic; Epidemiologic Studies; Etiology; Exposure to; fetal; Fetus; Genes; Genetic; Health; Heavy Metals; Human; Immune system; in utero; Investigation; Lead; Life; Literature; longitudinal design; Manganese; Measurement; Measures; mercury; Metal exposure; Metals; Methodology; Methods; mineralization; Mothers; neurodevelopment; Neurodevelopmental Disorder; Nickel; novel; Perinatal; Perinatal Exposure; Play; postnatal; Predisposition; Pregnancy; prenatal; Property; prospective; public health relevance; Recording of previous events; repository; Risk; Risk Factors; Role; Sampling; skeletal; Staging; Time; Tissues; Tooth structure; Toxic Environmental Substances; toxicant; Toxicant exposure; Work

MMS, now trying to scam the Irish

15 Jul

MMS. Magical Mineral Solution. CD. Chlorine Dioxide protocol. It has many names. And it’s a scam. Hiding behind a “church”. And now the Irish get to battle this.

Magic Mineral Solution isn’t magic and it isn’t a mineral solution. It’s a bleach. And among the various scams is the idea that if you force your autistic kid to drink this bleach or take this bleach as an enema, you can cure your child’s autism.

The Irish Examiner has a story: ‘Miracle solution can cure autism’. It’s about how the proprietor of the “church” that is pushing MMS telling an Irish mother that it is a “fact” that MMS can cure autism….and asking for a hefty donation.

When Ms O Leary asked if MMS “could really cure autism”, she alleges Mr Christopher replied it was not a possibility but a fact — a claim also made about numerous conditions on the Genesis II Church website.

Ms O Leary was then sent an email, giving directions to the seminar, and asking her for a €295 donation.

And also:

In 2012, after three hospital admissions and other incidents linked to MMS, Dr Naren Gunja of New South Wales’ Poisons Information Centre in Australia told the Sydney Morning Herald: “It’s a bit like drinking concentrated bleach. They’ve had corrosive injuries: vomiting, stomach pains, diarrhoea.

“If you drink enough sodium chlorite it causes kidney problems, it could cause death.”

By the way, if someone tells you that MMS isn’t a bleach, yeah, it’s a bleach. Calling it “CD” doesn’t change that.

And if they say it’s safe, they are wrong. If they say it cures autism. Run. Here’s a bit from a recent FDA warning:

•Miracle Mineral Solution. Also known as Miracle Mineral Supplement and MMS, this product becomes a potent chemical that‘s used as bleach when mixed according to package directions. FDA has received reports of consumers who say they experienced nausea, severe vomiting and life-threatening low blood pressure after drinking the MMS and citrus juice mixture.

Irish Central has: Irish warned of poisonous ‘miracle cure’ being peddled by US church (VIDEO). I feel both sad that we in the U.S. didn’t stop this nonsense before it exported to Ireland…and jealous that the Irish and their newspapers are quick to spread the word about MMS.

And, back at the Irish Examiner: Drugs watchdog investigating ‘miracle’ cure.

Ireland’s drugs watchdog is investigating at least two people based in this country who are believed to be selling or administering a “miracle” cure for serious conditions, which is in reality a potent bleach.

The Irish Independent: Irish patients warned ‘miracle cure’ from US church is bleach. And the Southern Star has Warning about Genesis II Church.

MMS got it’s foothold in the autism community through the AutismOne conferences. Here in the U.S., gatherings like AutismOne sell all manner of faux therapies for autism. AutismOne will take just about anyone’s money to present a cure, especially if it is sold as healing “vaccine injury”.

So, with apologies to Ireland. We know this is a scam, but we can’t stop it here. I wish you better luck. Be grateful that your press has jumped to inform you. Our press is still trying to figure out if keeping disabled children from being forced to drink bleach is a worthwhile story.


By Matt Carey

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