Unlock Autism

Research: “The Myelin Project”:

The exciting work of researchers funded by The Myelin Project, whose goal is to remyelinate the human central nervous system, may someday have benefits for autistic children. Only time will tell if a specific area of damaged neurons can be found and potentially repaired with stem cells.

The first human trial, conducted by Dr. Timothy Vollmer at Yale University School of Medicine, will attempt to transplant myelin-forming Schwann cells into the brains of five patients with multiple sclerosis. The cells will be obtained from the sural nerves of the patients themselves. Although Schwann cells normally produce myelin in the peripheral nervous system, several recent experiments conducted on rodents and cats have shown these cells have the ability to remyelinate in the CNS as well.

While multiple sclerosis is a long way from autism, there is discussion of anti-myelin antibodies in autism, and there is talk of inflammatory processes involving myelin. Whether this technology can help autism if it works for multiple sclerosis is anybody’s guess, but it’s exciting to wonder about.

The Myelin Project funds a Cell Culture Unit at the University of Wisconsin-Madison, where Dr. Su-chun Zhang continues to generate cultures with ever-higher percentages of human oligodendrocyte precursors (OPs). Oligodendrocytes are the cells that normally myelinate the CNS. If obtainable in sufficient quantity, they would provide an alternative to Schwann cells for transplantation. The Unit has developed a method to track transplanted OPs by MRI, labeling the cells with iron particles. In another recent experiment, Dr. Baron-Van Evercooren and colleagues were able to remyelinate as many as 55% of the nerves in monkey spinal cord lesions by transplanting the monkeys’ own Schwann cells. These initial positive results, however, have not been confirmed in subsequent attempts. She suspects that the viral labels she used to distinguish the transplanted cells caused them to die. She is trying again without viral labeling. If successful, this experiment would prove that CNS remyelination is feasible in higher animals.

Several researchers funded by The Myelin Project have injected myelin-forming cells into the ventricles of the brain of experimental animals and have shown that these cells were transported by the cerebrospinal fluid to all regions of the brain. This makes it more likely that injected cells will travel to where the myelin needs to be repopulated.

The Myelin Project has funded Dr. Oliver Br�stle of the University of Bonn, Germany, and Dr. Evan Snyder of Harvard University to work with neural stem cells (NSC). These are self-renewing, multipotent cells, capable of differentiating into the major types of neural cells, including oligodendrocytes. One of their most potentially beneficial properties is their tendency to respond to signals in the CNS environment. In CNS diseases, these signals guide the cells to damaged areas. Second, they prompt them to differentiate into the specific cell type needed for the repair — neurons in nerve diseases like Parkinson’s and oligodendrocytes in myelin disorders like the leukodystrophies and multiple sclerosis.

NSCs are typically of fetal origin, but have also been found in the adult brain. NSCs can be multiplied in culture indefinitely as an “immortal” cell line. They could eventually provide an inexhaustible source of myelin-forming cells, eliminating the need for obtaining them from fresh tissue. Several research centers are now testing human NSCs to verify their safety and in particular to rule out any risk of their becoming cancerous. If this testing concludes favorably, then prospective myelin repair strategies could take a two-fold approach. NSCs would be injected into the ventricular system where the cerebrospinal fluid would circulate them to all parts of the CNS. Local signals would then come into play, guiding the cells to the specific demyelinated areas.

The Myelin Project has also funded Dr. Robin Franklin of the University of Cambridge to study olfactory ensheathing cells, a third type of myelin-producing cell. He has perfected a technique for demyelinating the area of rat brain connecting the cerebellum with the brain stem. He subsequently remyelinated the area by transplanting rat Schwann cells, which adds to the body of evidence in favor of Schwann cell transplantation as a way of repairing CNS myelin lesions.

The Myelin Project has also funded Dr. Inderjit Singh of the Medical University of South Carolina to study the use of Lovastatin in the treatment of myelin disorders. The drug corrects the biochemical defect of adrenoleukodystrophy, lowering the levels of very long chain fatty acids in plasma. Preliminary studies with an animal model of MS have confirmed Lovastatin’s ability to block the induction of cytokines, substances responsible for the inflammation of the CNS. We know that the levels of very long chain fatty acids and of some cytokines are elevated in autism. I am wonderijng already if Lovastatin might be worth trying for children with documented elevated very long chain fatty acids and elevated cytokines.

These studies present exciting possibilities for the future for treating neurodegenerative diseases. They may eventually have relevence for such diverse conditions as autism, cerebral palsy, and CNS vaccine damage syndromes. Time will tell.

find more at http://www.healing-arts.org/children/cell.htm

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Where as I appreciate any and most attention Autism receives, I feel a bit sickened by the fact that celebrity’;s seem to be leanding their names solely for the purpose of publicity.

Jenny is cool, but her book talks about she is able to afford the therapy’s that most of us only dream of or mortgage our homes for.  the therapy’s she mentions in the book are not hers, they are those of Berdard and Tomatis. Deidre Imus was a big factor in passing the Combating Autism Act, which is a lame act of empty promises. Where is she now? Robert Kennedy, now I was shocked to see how much attention he gets for helping Autism get reserach dollars, I thought he was an enviormentalist? And what is President Bill; Clintoln doing rasing money for children in far off lands, most of which wil never even see the dollasr raised when 1 in 150 children in the US are diagnosed with Autism, shame on you Bill! I don’t know, maybe I am wrong here and maybe, just maybe getting celebrity endorsement is better than none, but what have we gained since Autism is such a celebrity cause? A few best sellers or rehashed gobblee goop?

This is not a part time thing here, this is a life long condition and for most finanacial burden. What do we have to do, go on TV and get sponsors for individual families here in the states? We need insurance reforms like we see taking place in a few states like New Jersey, we need the medical community to rally here. Autism is horrible and the numbers climb ever day, why is it not being treated as an epidemic, but rather as a celebrity attention grabber!!?? What are your thoughts. Please share them and lets take the bull by the horns ourselves and Unlock Autism.

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We could use a hand in finding material to share with others like you. If you have an experiences or know of other great resources for information, Please leave some comments or write to us at info@unlockautism.com This site is for us all. We are trying to direct you to pertinent information about Autism. Success stories and information about therapy’s and diets which helped or those which didn’t. Keep in mind, not all therapy’s will work for all. Autistic people are individuals in the truest sense of the word, with loving and caring families trying to unlock autism and let that person out.

If we can gather enough stats and information, perhaps we can help others. For us personally, Its been a whole lot of Love, Therapy’s and at times Snake Oil. Whats worked for us has been, ABA, Signing Time, Auditory Integration and Omega’s plus the usual OT, PT and Speech. But also encouraging more social engagement.

All I know is that we as parents know what works and what doesn’t, lets help those who are just discovering Autism. Let us help each other from being fooled by the latest and greatest therapy’s promising miracle and instant cures.
If you are interested in getting involved with UnlockAutism.com, let us know and share your wisdom.

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Original Article Found on TranslatingAutism.com You can find a more complete description and review of this paper based on the press coverage here. Thus, I’ll limit this to a micro summary and a few related thoughts. The researchers wanted to experimentally test the hypothesis that exposure to maternal neuronal antibodies (IgG) during the PREnatal period could be one of the causes of at least some variants of Autism. To test this hypothesis the researchers exposed 4 prenatal rhesus monkeys with IgG taken from human mothers who had multiple children with ASD. They also exposed 5 prenatal monkeys with IgG taken from human mothers who did not have any children with Autism. Once the monkeys were born, these two groups were also compared to monkeys that had not been exposed to any antibodies. The researchers found that the monkeys that had been exposed to the antibodies of human mothers of children with autism engaged in much higher levels of unique whole-body stereotypic behaviors and less social contact with familiar peers, than did the monkeys exposed to IgG of mothers of typically developing kids or monkeys not exposed to any antibodies. Furthermore, these stereotypic behaviors increased when the monkeys were exposed to novel environments or peers. As I understand how controversial this paper will be for some people, I want to say that the authors are very clear and explicit in stating that this is NOT an animal model of autism. That is, they did not intent to say that they were able to “cause” autism in these monkeys via exposure to IgG. Instead, their data presents some evidence that exposure to IgG before birth leads to unique patterns of stereotypic behaviors, similar to those observed in some children with ASD. This is a very small preliminary study, but the results are fascinating in that it will guide future research to explore exposure to IgG as a potential cause (one of many) of ASD.

Seems plausible since the IgG antibodiy can get through the placenta to protect the baby..but much more work needs to be done first. For more on IgG http://en.wikipedia.org/wiki/IgG

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From Age of Autism – What will happen to the Monkees ?

The first research project to examine effects of the total vaccine load received by children in the 1990s has found autism-like signs and symptoms in infant monkeys vaccinated the same way. The study’s principal investigator, Laura Hewitson from the University of Pittsburgh, reports developmental delays, behavior problems and brain changes in macaque monkeys that mimic “certain neurological abnormalities of autism.”

The findings are being reported Friday and Saturday at a major international autism conference in London.

Although couched in scientific language, Hewitson’s findings are explosive. They suggest, for the first time, that our closest animal cousins develop characteristics of autism when subjected to the same immunizations – such as the MMR shot — and vaccine formulations – such as the mercury preservative thimerosal — that American children received when autism diagnoses exploded in the 1990s.

The first publicly reported results of this research project come in both oral and poster presentations on Friday and Saturday at the International Meeting For Autism Research in London. Poster presentations must go through a form of peer review before they are presented at the conference; the papers have not yet appeared in a scientific journal.

In addition to Hewitson’s oral presentation today, on Saturday in one of two related poster presentations, the researchers also are reporting in their abstract that “vaccinated animals exhibited progressively severe chronic active inflammation [in gastrointestinal tissue] whereas unexposed animals did not. We have found many significant differences in the GI tissue gene expression profiles between vaccinated and unvaccinated animals.” Numerous scientific studies, as well as many parents, report severe GI ailments in children with regressive autism.

The results are sure to be controversial, in part because they lend credence to studies first published in 1998 by British pediatric gastroenterologist Andrew Wakefield, one of Hewitson’s co-authors on these findings. He described an unusual inflammatory bowel condition in children who had regressed into autism after they received the measles-mumps-rubella (MMR) vaccination. Wakefield is currently fighting charges of medical misconduct in Britain over allegations of conflict-of-interest and improper procedures related to that paper. He denies the charges.

In the program for the conference, the 7th Annual International Meeting for Autism Research (IMFAR), there are three separate presentations listed that report results from the overall research program. The first, an oral presentation entitled “Pediatric Vaccines Influence Primate Behavior, and Amygdala Growth and Opioid Ligand Binding” (the “amygdala abstract”) was led by Dr. Hewitson and lists 12 co-authors, including five of her colleagues from the University of Pittsburgh and Dr. Wakefield. Other authors are chemists, pathologists and psychologists from the universities of Kentucky, California-Irvine, and Washington.

Hewitson’s introductory presentation will be followed by two poster presentations on Saturday; one of the two, “Pediatric Vaccines Influence Primate Behavior, and Brain Stem Volume and Opioid Ligand Binding”, was led by Wakefield and includes six additional co-authors.

It focuses on the developmental effect of vaccine exposures on brain growth during infancy. The second, “Microarray Analysis of GI Tissue in a Macaque Model of the Effects of Infant Vaccination,” was led by Steven Walker of Wake Forest University and performed gene array analysis on the intestinal tissues of the vaccinated and unvaccinated monkeys.

The studies address – albeit in animals, not children — one of the major criticisms by parents and scientists concerned about a possible link between the greatly stepped-up immunization schedule in the 1990s, including higher exposure to the mercury preservative, and autism. While the Food and Drug Administration approves individual vaccines as safe and effective, and an advisory committee to the Centers for Disease Control and Prevention recommends the childhood immunization schedule adopted by the states, the overall health outcomes from the total vaccine load, versus no vaccinations at all, have never been compared, the authors said.

A bill requiring the government to conduct a study of autism rates in unvaccinated American children is pending in the U.S. House of Representatives, co-sponsored by Reps. Carolyn Maloney (D-N.Y.) and Tom Osborne (R.-Neb.). Just this week, former National Institutes of Health Director Bernadine Healy called for more research into a possible vaccine link to autism and said the question had not been settled, despite repeated assertions to that effect by the CDC, the Institute of Medicine and the American Academy of Pediatrics.

In the abstract for today’s oral presentation, the authors noted that macaques, the type of monkey used in the study, “are commonly used in pre-clinical vaccine safety testing, but the combined childhood vaccine regimen, rather than individual vaccines, has not been studied. Childhood vaccines are a possible causal factor in autism, and abnormal behaviors and anomalous amygdala growth are potentially inter-related features of this condition.”

The study found evidence of both behavioral and biological changes after the 13 macaque monkey infants were administered proportional doses, adjusted for age, of the vaccines recommended between 1994 and 1999. Three monkeys were not given any vaccines.

“Primate development, cognition and social behavior were assessed for both vaccinated and unvaccinated infants using standardized tests developed at the Washington National Primate Research Center.” MRI and PET scans looked for brain changes after administration of the MMR.

“Compared with unexposed animals, significant neurodevelopmental deficits were evident for exposed animals in survival reflexes, tests of color discrimination and reversal, and learning sets,” the authors reported. “Differences in behaviors were observed between exposed and unexposed animals and within the exposed group before and after MMR vaccination. Compared with unexposed animals, exposed animals showed attenuation of amygdala growth and differences in the amygdala binding of [11C]diprenorphine. Interaction models identified significant associations between specific aberrant social and non-social behaviors, isotope binding, and vaccine exposure.”

One of the Saturday abstracts makes the further point that the research “revealed significant differences between exposed and unexposed animals” in the kinds of developmental behaviors a mother might be able to observe, “with delayed acquisition of root, suck, clasp hand, and clasp foot reflexes.” They conclude by noting that “This animal model examines the neurological consequences of the childhood vaccine regimen, Functional and … brainstem anomalies were evident in vaccinated animals that may be relevant to some aspects of autism. The findings raise important safety issues while providing a potential animal model for examining aspects of causation and disease pathogenesis in acquired neurodevelopmental disorders.”
–
Dan Olmsted is Editor of Age of Autism.

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Researchers from the Massachusetts Institute of Technology (MIT) have recently generated a mice model for autistic savants – a phenomenon in which an autistic person has an outstanding skill alongside his poor ability in social interactions. By using genetically engineered mice in which a specific protein in the brain was inactive, the researchers discovered an enhanced learning ability of the mice, but also an impaired long term memory, which resembles autism characteristics. The scientists hope that in the future, this work will lead to the development of treatment for autism and for other brain development disorders.
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Seems a bit like covering one’s tracks here. Seizures and Autism commonly go – hand in hand and can trigger serious health issues which lie dormant in the body.

Written and owned By Michael Smith, North American Correspondent, MedPage Today Published: March 14, 2008

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

ATLANTA, March 14 — An apparent increased risk of febrile seizures has led the CDC to soften one of its recommendations on immunizing children against measles, mumps, rubella, and varicella with a combination vaccine.

The agency had said the combination tetravalent vaccine against the four diseases (ProQuad) was to be preferred over vaccination with a trivalent measles, mumps, and rubella vaccine at the same time as a separate varicella shot.

That preferential recommendation has been withdrawn. The agency’s Advisory Committee on Immunization Practices (ACIP) now says there should be no preference, the CDC said in the March 14 issue of Morbidity and Mortality Weekly Report.

The change comes after review of data from the Vaccine Safety Datalink, which monitors vaccine safety, as well as preliminary results from a post-licensing study conducted by Merck, which makes the tetravalent vaccine.

The Vaccine Safety Datalink, the CDC said, showed a signal of increased risk for seizure among children ages 12 to 23 months who were given the tetravalent vaccine, compared with those who got the trivalent vaccine.

The increased rates were seen seven to 12 days after vaccination.

Once the signal was seen, the agency said, analysts used the Vaccine Safety Datalink for a study comparing seizure rates among children who got the tetravalent vaccine and those who got a trivalent vaccine plus a varicella vaccine at the same visit.

The analysis included 43,353 children ages 12 to 23 months who received the tetravalent vaccine and 314,599 who received the trivalent vaccine and varicella vaccine at the same visit.

The researchers reviewed medical records to validate the diagnosis and used a multivariate logistic regression to adjust for age and influenza season, the CDC said.

Results of that analysis showed:

* A rate of nine febrile seizures per 10,000 vaccinations among recipients of the tetravalent vaccine.
* The rate was four per 10,000 vaccinations among those who got the trivalent vaccine along with the varicella vaccine.
* The adjusted odds ratio was 2.3, with a 95% confidence interval from 1.6 to 3.2, which was significant at P<0.0001.
* Of the 166 children who had febrile seizures after vaccination and had hospitalization information available, 26 (or 16%) were admitted to a hospital.
* There were no deaths.

The advisory committee was told that interim data from the Merck post-licensing study showed a similar relative risk for seizure, although the difference did not reach statistical significance. Only about half of the final sample size needed was available for the analysis.

Neither study looked at the risk of a febrile seizure after the second recommended dose of the vaccine, at ages four through six years.

The CDC noted that the tetravalent vaccine is currently in short supply in the U.S., because of manufacturing problems not related to safety, and is not expected to be widely available before 2009.

The agency also said that febrile seizures are not uncommon in children and generally have an excellent prognosis.

Additional source: CDC
Source reference:
CDC “Update: Recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine” MMWR 2008; 57(10): 258-60.

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By Todd Neale, Staff Writer, MedPage Today
Published: February 07, 2008
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

LONDON, Feb. 7 — A community-based case-control study found no relationship between the measles-mumps-rubella (MMR) vaccine and autism spectrum disorders, researchers reported here.

“No difference was detected in the distribution of measles antibody or in measles virus in [autism spectrum disorder] cases and controls whether the children had received the first, second, or both MMR vaccinations,” Gillian Baird, Ph.D., of Guy’s and St Thomas’ NHS Foundation Trust, and colleagues wrote online in the Archives of Disease in Childhood.

This study reinforces the findings of two case-control studies published last year and three epidemiological studies published since 1999 that also failed to make any connection between the vaccine and autism spectrum disorders.

Analyzing a cohort of children born from July 1, 1990 through Dec. 31, 1991 in the South Thames region of England, the researchers tested the hypothesis that the MMR vaccine contributed to the pathogenesis of autism spectrum disorders, “as evidenced by signs of a persistent measles infection or abnormally persistent immune response.”

Using various diagnostic criteria, Dr. Baird’s team recruited 98 children with autism spectrum disorders. They were divided into those with broad disorders (66) and those with narrow autism (32).

The researchers also recruited two control groups. One comprised 52 children with special educational needs but no signs of autism spectrum disorders, and the other, 90 children who were developing normally.

All participants had blood drawn and all had had at least one MMR vaccination.

The researchers tested for a persistent measles infection in peripheral blood mononuclear cells because viral replication occurs here during acute infection and has been reported to contain measles genome in a small number of autistic children. They used three reverse transcriptase PCR assays. Samples were tested to ensure that they were adequate by using a β2 microglobulin housekeeping gene PCR with a sensitivity of 10 genome copies per reaction mixture.

All samples were negative for the first two assays. On one of the assays — the M gene PCR — three samples were reactive for measles virus, with one sample from the narrow autism group containing the C2 strain and two from the normally developing control group containing the D6 strain. All three samples were negative when retested.

The researchers proposed two explanations for the initial positive finding: laboratory cross-contamination or incomplete immunity, which can allow measles virus to be found in asymptomatic people.

Dr. Baird’s team then tested the blood samples for measles IgG antibody with the plaque neutralization test to look for evidence of an abnormal immune response. There was no difference in IgG antibody levels between those with one or two MMR vaccinations (difference=0 log10 (mIU/mL), 95% CI -0.12 to 0.11, P=0.94).

There were no significant differences between the antibody levels in either autism spectrum disorder group or either of the control groups (P=0.13). Differences did not reach statistical significance when those with one or two vaccinations were analyzed separately (P=0.20 and P=0.66, respectively).

The combined control group of special educational needs and normally developing children did not have significantly lower levels of antibodies than those for the narrow autism (P=0.45), broad disorder (P=0.29), or combined autism/broad disorder (P=0.27) groups.

Some level of regression — either the loss of five or more words used communicatively during a three-month period or a regression of words or skills in communication or play behavior — was reported in 23 children in the broad disorders group but antibody levels were not significantly higher than those in the combined control group (P=0.18).

The researchers acknowledged limitations to the study, including the fact that the participants in the normal development control group were not randomly selected.

Also, parents were informed that the study was about MMR vaccination, which may have biased those who signed up to participate.

The researchers noted that only 29% of children with a local diagnosis of autism spectrum disorders received a second MMR vaccination, compared with 50% of those without such a diagnosis, a finding that “is of public health relevance. … This may reflect parental concern about vaccination following a diagnosis of developmental abnormality.”

The study was funded by the Department of Health, the Wellcome Trust, the National Alliance for Autism Research, and Remedi.

Dr. Baird has acted as an expert witness for the diagnosis of autism. Two co-authors have given unpaid advice to lawyers, and another has served as an expert witness, in MMR and MR litigation. Another co-author receives royalties from diagnostic tools used in this study.

Primary source: Archives of Disease in Childhood
Source reference:
Baird G, et al “Measles vaccination and antibody response in autism spectrum disorder” Arch Dis Child 2008; DOI: 10.1136/adc.2007.122937.

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What is SEED?

SEED stands for the Study to Explore Early Development. It is a 5-year, multi-site collaborative study that will help identify what might put children at risk for autism spectrum disorders (ASDs) and other developmental disabilities. It is being conducted by six study sites and a data coordinating center called the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network.

What are the six CADDRE centers?

The six CADDRE centers are:

* California CADDRE: Kaiser Permanente Division of Research and the California Department of Health Services
* Colorado CADDRE: Colorado Department of Public Health and Environment and the University of Colorado at Denver and Heath Sciences Center
* Georgia CADDRE: the National Center on Birth Defects and Developmental Disabilities
* Maryland CADDRE: Johns Hopkins University and Kennedy Krieger Institute
* North Carolina CADDRE: University of North Carolina at Chapel Hill
* Pennsylvania CADDRE: University of Pennsylvania School of Nursing and The Children’s Hospital of Pennsylvania

Where exactly is SEED being conducted?

California

a two county area: Alameda and Santa Clara counties

Colorado

the seven-county Denver metropolitan area: (Arapahoe, Adams, Boulder, Broomfield, Denver, Douglas, and Jefferson counties).

Georgia (CDC)

the five-county metropolitan Atlanta area: Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties.

Maryland

seven jurisdictions in northeastern Maryland: Anne Arundel, Baltimore, Carroll, Cecil, Harford and Howard Counties and Baltimore City.

North Carolina

a ten county area: Alamance, Chatham, Davidson, Durham, Forsyth, Guilford, Johnston, Orange, Randolph, and Wake counties.

Pennsylvania

three counties: Chester, Montgomery and Philadelphia counties.

*CDC also funds Michigan State University to run the study’s Data Coordinating Center and Johns Hopkins University to run the study’s central laboratory.

How were the sites selected?

The sites were originally picked through an open competitive review process in 2001 and funded for 5 years. The sites were selected based on the merit of their application. In 2006, CDC had a limited competitive review process and funded the sites for another 5 years.

How can I enroll my child into the study?

The study is a population based study – meaning that the participants will be recruited from all children and families in each study community who meet certain criteria rather then focusing on individuals at a specific clinic or school. Families of children with specific developmental conditions, as well as a random sample of all children born in the community will be invited to participate. If the invited family is interested, then we ask some questions to determine if they are eligible, and if they are eligible then the family is enrolled.

Can I sign my child up for this study?

Although families can self-refer to participate in this study, they have to fulfill certain criteria in order to be eligible. Some families who self refer may not be eligible. Our goal is to send letters of invitation to all families who may fulfill the eligibility criteria. By sending letters of invitation to as many eligible families as possible, we hope to enroll a representative sample of families in each study area.

Examples of the study eligibility criteria include – the child must be born within the study period, the child must be born and still living in the study area, they must have a legal guardian, they must know English or Spanish (although these vary by site), and they must also meet certain diagnostic criteria.

What will each study participant have to do?

Each parent or caregiver will have to answer questions about their child’s development and their family’s medical history. The study clinicians will perform a brief exam and developmental tests on the child. Each parent and child will have to give small samples of blood, cells from inside the mouth, and a sample of the child’s hair. Finally, we would access the mother’s and the child’s medical records.

Why are we only looking at children in 6 states?

The funding for the study allowed us to support 6 study sites around the country.

Why are we only looking at children between the ages of 2-5?

The study will focus on children who are 2 to 5 years old. This age range was selected to reduce the amount of time since pregnancy and early development so that parent recall of events during these time periods is better, so that medical information is easier to retrieve, so that families are less likely to have moved away from the study area, and it will also be nearer the beginning of treatment for children in developmental intervention programs.

What is being investigated, and why?

* Physical and behavioral characteristics – Autism is a complex disorder and we want to better understand the full range of characteristics that are associated with autism. In this way, we may also better understand how the different causes of autism may be associated with specific subgroups of children within the autism spectrum.
* Infection and immune function, including autoimmunity – We want to follow up on reports that infections, or an abnormal response to infection – called the body’s immune response – may increase the risk for autism.
* Reproductive and hormonal features – We want to follow up on reports that abnormal hormone function – perhaps in the mother when she is trying to get pregnant, or later during pregnancy, or even later in the child after birth – may be associated with autism.
* Gastrointestinal features – We want to follow-up on reports that children with autism have abnormal gastrointestinal function, and whether it may be related to the causes of autism.
* Genetic features – Autism is a highly genetic disorder, but in particular we want to see if the genes that may be related to risk factors we are investigating – such as the genes that control immune function – are associated with autism.
* Socio-demographic features – We want to better understand the social, demographic, and economic features of families that are associated with having a child with autism.
* Smoking and alcohol use in pregnancy – Substance use in pregnancy can potentially harm the developing fetus and so we want to see if these so-called lifestyle factors are associated with autism.
* Sleep features – We want to follow-up on reports that children with autism have abnormal sleep patterns.
* Select mercury exposures – There are several studies, including studies funded by the government, looking at environmental exposures related to autism including mercury. CADDRE didn’t want to duplicate the work of these other studies, but we chose to look at information on vaccines and other types of medical procedures that may have mercury exposure that we can get through medical records.
* Occupational exposures – There are several studies, including studies funded by the government, looking at environmental exposures related to autism including mercury. CADDRE didn’t want to duplicate the work of these other studies, but we chose to ask parents to report to us about possible exposures they may have had at their jobs.

We selected these research factors after an extensive review of the literature. We designated each of the factors as high priority based on the how strongly they seemed to be associated with ASD and what new information we needed to collect about each factor, balanced by how well we could study each factor with our particular study methods.

What “selected mercury exposures” will be studied? How will they be studied? Why were these selected?

The mercury exposures we are looking at relate to vaccines or other medical treatments that are being studied include – vaccines that the mom received during pregnancy, the child’s vaccine exposures after birth and specific other factors such as RhoGAM treatment in pregnancy if the mom has developed an immune response against the fetus that can harm it.

There are several studies, including studies funded by the government, looking at environmental exposures related to autism including mercury. SEED didn’t want to duplicate the work of these other studies, but since we are getting medical records, we choose to look at information on vaccines and other types of medical procedures that may have mercury exposure that we can get through medical records.

Will the study include vaccines as a potential cause of autism?

Yes, the study will include vaccines. The mercury exposures being studies include – vaccines that the mom received during pregnancy, the child’s vaccine exposures after birth and specific other factors such as RhoGAM treatment in pregnancy if the mom has developed an immune response against the fetus that can harm it.

There are several studies, including studies funded by the government, now looking at environmental exposures in autism such as mercury. SEED doesn’t want to duplicate the work of these other studies, but since we are getting medical records, we choose to look at information on vaccines and other types of medical procedures that may have mercury exposure that we can get through medical records.

Will CDC find out if thimerosal causes autism?

It is too soon to speculate on the results of the study. We hope the study will give us a better idea of which of the risk factors that we will be looking at seem to be the most important in causing autism.

If the study shows that thimerosal is a cause of autism, will CDC report the data? What guarantees does the public have that the findings won’t be covered up?

We will report all the findings of the study by following the normal scientific review process as soon as possible.

When the study is completed, will we know the causes of autism?

It is too soon to speculate on the results of the study. We hope the study will give us a better idea of which of the risk factors that we will be looking at seem to be the most important in causing autism. The causes may be related to genes, the environment, or a relationship between the two – such as if some groups of children with certain genes are more easily harmed by some environmental exposures.

Will this study find a prevention/cure for autism?

It is too soon to speculate on what we might find about the causes of autism. But, we are hopeful that the findings from SEED will help the development of future studies specifically designed to assess treatments among children with autism.

What are the other developmental disabilities being studied?

We will be studying a range of other developmental disabilities, including mental retardation, developmental delay, and other behavioral problems in early childhood.

Why are we looking at other developmental disabilities?

By comparing children with autism and children with other developmental disabilities we will try to see if the risk factors we observe in children with autism are unique to autism or if they are also important in children with other developmental problems.

Looking at children with other developmental disabilities will also provide a way of comparing responses of children with developmental disabilities, in general, versus typically developing children.

How will you get the names of children to invite into the study?

We are working with our partners in the community who serve children with developmental problems and through these partners we will be sending out letters to families to invite them to participate.

Why didn’t or doesn’t the 2001/2002 funding represent “the first national study”?

In the initial grant awards (2001/2002), the grantees were responsible for 3 activities: setting up monitoring programs for autism and other developmental disorders, collaboration on the multi-site epidemiologic study, and investigator-initiated special studies. Although the multi-site study was planned, funding levels were not adequate to implement the multi-site study during the 2002/2002 funding cycle. Consequently, implementation was delayed until the current funding cycle. All funds awarded to the grantees in the current grant cycle are dedicated to implementation of the multi-site study. The grantees competed for funding to continue their monitoring activities under a separate grant announcement earlier in 2006, and no funding will be available for investigator-initiated special studies.

In what way(s) will the sample populations be representative of all children?

It seems that by not including major states like New York, Illinois, Texas, etc. it’s hard to claim this is “nationally representative”? Further, how will the selection/recruitment processes ensure or foster generalizability?

The two groups of children with ASD and other developmental problems will be identified in multiple clinical and educational facilities in each community to insure that the participants are representative of all children with these types of developmental problems – and not just children who might be seen at a single clinic or intervention program. The third group of study children will be randomly selected from all children born in each community during the same time period so that they are representative of all children in the study area most of whom do not have developmental problems.

Although resources do not permit the sample to be drawn so that it is statistically representative of all children in the nation, by conducting the study in 6 different geographic areas across the country with diverse populations and by identifying children from multiple sources in each community we hope to have a study sample that more closely represents children with ASD, other developmental problems, and typical development across the country.

Will there be interim results or will the study first have results six or so years from now?

Many of the core study hypotheses will require that we have data collection completed on the full study sample before analysis can take be completed, but some interim analyses that require less than the full study sample may be possible. We don’t want to rush interim analyses, however, before we have a good representative sample of children.

What do you mean by “community diversity”?

SEED is located in select study areas within 6 states: 2 counties in the San Francisco, California area, 7 counties in the Denver, Colorado area, 5 counties in the Atlanta, Georgia area, 7 counties in the Baltimore and northeast Maryland area, 10 counties in central North Carolina, and 3 counties in the Philadelphia, Pennsylvania area.

These study areas include diverse communities and populations from which study participants will be drawn.

Can this really be classified as a national study since it only involves six states?

It is a multi-site study set in diverse communities in 6 locations around the country: California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania.

Although resources do not permit the sample to be drawn so that it is statistically representative of all children in the nation, by conducting the study in 6 different geographic areas across the country with diverse populations and by identifying children from multiple sources in each community we hope to have a study sample that more closely represents children with ASD, other developmental problems, and typical development across the country.

How will this give us national insight?

Compared to a study located in a single area, our study in six different areas gives us geographic and community diversity that will give us greater insights into the variability of who is at risk and what are the risk factors for autism.

What is the methodology for collecting the data? Same for each state?

Yes, all the sites are using a common study protocol – meaning they are following the same procedures for recruiting participants and collecting data so that, at the end, the data from all 6 sites can be pooled into a single large data base for analysis.

We will be asking participants to complete self-administered questionnaires; interviewing mothers about pregnancy-related issues and developmental conditions in their children; conducting a developmental exam of each study child to evaluate cognitive and

emotional development, language and adaptive skills, and motor skills, and a dysmorphology exam of the child (that will look at physical features that may indicate an underlying genetic condition); taking cheek swab and blood samples from the mother; father, and child; taking a hair sample from the child; and looking at the mother and child’s medical records.

Do all 2,700 of the children have an ASD?

No, there will be 900 children in each of 3 groups: children with ASDs, children with other developmental problems, and children drawn from the community most of whom are typically developing.

I live in one of the states with a CADDRE center. Who can I contact for more information about the study?

California CADDRE
Kaiser Permanente Division of Research
California Department of Health Services
Oakland, CA
510.620.3700

Colorado CADDRE
Colorado Department of Public Health and Environment
University of Colorado at Denver and Heath Sciences Center
Denver, CO
303.315.0066
303.692.2680

Georgia CADDRE
National Center on Birth Defects and Developmental Disabilities
Atlanta, GA
404.498.3800

Maryland CADDRE
Johns Hopkins University
Kennedy Krieger Institute
Baltimore, MD
877.868.8014

North Carolina CADDRE
University of North Carolina at Chapel Hill
Chapel Hill, NC
919.966.2068

Pennsylvania CADDRE
University of Pennsylvania School of Nursing
The Children’s Hospital of Pennsylvania
Philadelphia, PA
215.573.2469
215.590.7474

Date: December 19, 2007
Content source: National Center on Birth Defects and Developmental Disabilities

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Nerve Cell Gene Linked to Autism
By Michael Smith, North American Correspondent, MedPage Today
Published: January 10, 2008
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

BALTIMORE, Jan. 10 — The risk for autism appears to increase in the presence of a common genetic variation on chromosome seven, especially when the condition is inherited from the mother, researchers here said.

The variant is a single nucleotide polymorphism (SNP) that’s found in 36% of the alleles of chromosome seven, according to Aravinda Chakravarti, Ph.D., of Johns Hopkins, and colleagues.

Dubbed rs7794745, the variant lies within a gene called contactin-associated protein-like 2 (CNTNAP2), Dr. Chakravarti and colleagues reported online in the American Journal of Human Genetics.

The gene, which encodes a protein involved in nervous system cellular interactions, had previously been associated with other neurological disorders, including cortical dysplasia-focal epilepsy and obsessive-compulsive disorder.

Also, two other papers in the journal reported links between autism and CNTNAP2. The reports come a day after researchers linked errors on chromosome 16 to the disorder. (See: Chromosome 16 Mutations Linked to Autism)

“CNTNAP2 is an excellent candidate gene for autism,” Dr. Chakravarti said.

“It encodes a protein that’s known to mediate interactions between brain cells and that appears to enable a crucial aspect of brain-cell development,” he added. “A gene variant that altered either of these activities could have significant impact.”

In a cohort of 72 families with multiple affected children — a total of 148 affected offspring and 292 other family members — the researchers performed a genome-wide scan for significant associations.

To reduce variation in the volunteers, the researchers required that the affected offspring meet a strict criterion of autism, rather than the broader “autism spectrum disorder.”

The gene scan found that a substitution of thymine for adenine at rs7794745 was significantly more common among those with autism (at P<2.14×10-5).

To confirm the finding, the researchers performed a separate genome-wide scan of 1,295 parent-child trios — this time with a broader definition of autism — and again found a significant over-transmission of the T allele (P<0.005) among the affected offspring.

Given the marked sex difference in autism — four times as many boys as girls are affected — the researchers also looked at which parent contributes the T allele to an autistic child.

The analysis found that the transmission frequency of the paternal T allele was 0.53 and the frequency of transmission of the maternal allele was 0.61, a difference that was significant at P<0.001, Dr. Chakravarti and colleagues said.

“This is a common variant,” Dr. Chakravarti said. “People inherit it all the time. Our finding that it’s associated with autism more often when it’s inherited from mothers is intriguing, but needs to be replicated.”

Meanwhile, using a language-based criterion — age at first word — another group of researchers found that a separate region of CNTNAP2 was associated with autism.

Daniel Geschwind, M.D., Ph.D., of the University of California at Los Angeles, and colleagues found that a SNP dubbed rs2710102 was significantly associated (P<0.028) with a delayed onset of speech.

In another study, researchers led by Matthew State, M.D., Ph.D., of Yale, found several rare variants in CNTNAP2 that appeared to be linked to autism.

Taken together, the three studies provide “unequivocal evidence” that disrupting CNTNAP2 leads to a subtype of autism spectrum disorder, said Dietrich Stephan, Ph.D., of the Translational Genomics Research Institute in Phoenix, in an accompanying commentary.

It’s now reasonable to say that people with autism combined with mutations in CNTNAP2 have “type 1 autism,” Dr. Stephan said.

The study was supported by the National Institute of Mental Health. Dr. Chakravarti did not report any potential conflicts.

Primary source: American Journal of Human Genetics
Source reference:
Arking DE, et al “A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism” Am J Hum Gen 2008; DOI: 10.1016/j.ajhg.2007.09.015.

Additional source: American Journal of Human Genetics
Source reference:
Stephan D, “Unraveling autism” Am J Hum Gen 2008; DOI: 10.1016/j.ajhg.2007.12.003.

Additional source: American Journal of Human Genetics
Source reference:
Alarcon M, et al “Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene” Am J Hum Gen 2008; DOI: 10.1016/j.ajhg.2007.09.005.

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