Re: Fw: [nsasa] Autism Speaks Video

March 31, 2007

And, for an ACTUAL voice of autism...

I find autismweeps despicable. Describing plotting

killing your kid isn't courageous. Doing everything

you can to silence ACTUAL AUTISTICS is disgusting.

Trying to buy out every autism org in the US is just

flat wrong.

And five for fighting is bigoted for agreeing to it,

and more bigoted for their pansyass " Im sorry you feel

that way " response to the writings of over a dozen

autistic adults saying how disgusted we were.

Autism speaks will NEVER speak for me. Over my cold

dead decaying body. They don't even NEED the money,

murdermomma made $125K from them in 2005. Think how

many STRUGGLING autism families that could have

helped. But it's all about THEM. Look at all their

EXPENSIVE galas.

Never. Never. Never. Eugenicists.

Send this one on to all your friends too.

Kassiane A. Sibley, autistic and proud since 1982

instigator of real autistic advocacy since before the

rich s had even HEARD of autism

--- wrote:

>

> Autism Speaks created a music video of the Five for

> Fighting song, " World " ,

> which features images of autistic children and their

> families.

> It is a truly moving video and was the work of Bill

> Shea.

> The band is generously donating $0.49 to Autism

> Speaks for each time the

> video is viewed - the funding goes toward research

> studies to help find a cure.

> When you have a moment, please visit the link below

> to watch the video and

> pass it along to your friends and family.

> They are aiming for 10,000 hits, but hopefully we

> can help them to surpass

> this goal.

>

_http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

>

(http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

>

> Thanks for your time.

>

> ************************************** See what's

> free at http://www.aol.com.

>

> [Non-text portions of this message have been

> removed]

>

> [Non-text portions of this message have been

> removed]

>

________________________________________________________________________________\

____

Food fight? Enjoy some healthy debate

in the Yahoo! Answers Food & Drink Q & A.

http://answers.yahoo.com/dir/?link=list & sid=396545367

March 31, 2007

And, for an ACTUAL voice of autism...

I find autismweeps despicable. Describing plotting

killing your kid isn't courageous. Doing everything

you can to silence ACTUAL AUTISTICS is disgusting.

Trying to buy out every autism org in the US is just

flat wrong.

And five for fighting is bigoted for agreeing to it,

and more bigoted for their pansyass " Im sorry you feel

that way " response to the writings of over a dozen

autistic adults saying how disgusted we were.

Autism speaks will NEVER speak for me. Over my cold

dead decaying body. They don't even NEED the money,

murdermomma made $125K from them in 2005. Think how

many STRUGGLING autism families that could have

helped. But it's all about THEM. Look at all their

EXPENSIVE galas.

Never. Never. Never. Eugenicists.

Send this one on to all your friends too.

Kassiane A. Sibley, autistic and proud since 1982

instigator of real autistic advocacy since before the

rich s had even HEARD of autism

--- wrote:

>

> Autism Speaks created a music video of the Five for

> Fighting song, " World " ,

> which features images of autistic children and their

> families.

> It is a truly moving video and was the work of Bill

> Shea.

> The band is generously donating $0.49 to Autism

> Speaks for each time the

> video is viewed - the funding goes toward research

> studies to help find a cure.

> When you have a moment, please visit the link below

> to watch the video and

> pass it along to your friends and family.

> They are aiming for 10,000 hits, but hopefully we

> can help them to surpass

> this goal.

>

_http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

>

(http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

>

> Thanks for your time.

>

> ************************************** See what's

> free at http://www.aol.com.

>

> [Non-text portions of this message have been

> removed]

>

> [Non-text portions of this message have been

> removed]

>

________________________________________________________________________________\

____

Food fight? Enjoy some healthy debate

in the Yahoo! Answers Food & Drink Q & A.

http://answers.yahoo.com/dir/?link=list & sid=396545367

March 31, 2007

Well, I'm not going to be quiet as vehement as Kassi, but that video

bugged me too. I mean, I'm all for raising awareness, and for

improving the lives of people with autism, and improving other

people's attitude towards it, but I also didn't like the implications

of a world without autism. I think the world would be a pretty boring

place with no autism at all.

I don't like the word cure. I don't think most of my kids need to be

cured of anything. All they need is to live their lives to their

fullest potential, while still being the quirky, adorable little

people that they are. Earlier diagnostics, better diagnostics, and

earlier/better intervention should be the goal. More realistic anyway.

Amnesty

>

> >

> > Autism Speaks created a music video of the Five for

> > Fighting song, " World " ,

> > which features images of autistic children and their

> > families.

> > It is a truly moving video and was the work of Bill

> > Shea.

> > The band is generously donating $0.49 to Autism

> > Speaks for each time the

> > video is viewed - the funding goes toward research

> > studies to help find a cure.

> > When you have a moment, please visit the link below

> > to watch the video and

> > pass it along to your friends and family.

> > They are aiming for 10,000 hits, but hopefully we

> > can help them to surpass

> > this goal.

> >

> _http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

> >

> (http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

> >

> > Thanks for your time.

> >

> > ************************************** See what's

> > free at http://www.aol.com.

> >

> > [Non-text portions of this message have been

> > removed]

> >

> > [Non-text portions of this message have been

> > removed]

> >

>

________________________________________________________________________________\

____

> Food fight? Enjoy some healthy debate

> in the Yahoo! Answers Food & Drink Q & A.

> http://answers.yahoo.com/dir/?link=list & sid=396545367

>

March 31, 2007

Well, I'm not going to be quiet as vehement as Kassi, but that video

bugged me too. I mean, I'm all for raising awareness, and for

improving the lives of people with autism, and improving other

people's attitude towards it, but I also didn't like the implications

of a world without autism. I think the world would be a pretty boring

place with no autism at all.

I don't like the word cure. I don't think most of my kids need to be

cured of anything. All they need is to live their lives to their

fullest potential, while still being the quirky, adorable little

people that they are. Earlier diagnostics, better diagnostics, and

earlier/better intervention should be the goal. More realistic anyway.

Amnesty

>

> >

> > Autism Speaks created a music video of the Five for

> > Fighting song, " World " ,

> > which features images of autistic children and their

> > families.

> > It is a truly moving video and was the work of Bill

> > Shea.

> > The band is generously donating $0.49 to Autism

> > Speaks for each time the

> > video is viewed - the funding goes toward research

> > studies to help find a cure.

> > When you have a moment, please visit the link below

> > to watch the video and

> > pass it along to your friends and family.

> > They are aiming for 10,000 hits, but hopefully we

> > can help them to surpass

> > this goal.

> >

> _http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

> >

> (http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

> >

> > Thanks for your time.

> >

> > ************************************** See what's

> > free at http://www.aol.com.

> >

> > [Non-text portions of this message have been

> > removed]

> >

> > [Non-text portions of this message have been

> > removed]

> >

>

________________________________________________________________________________\

____

> Food fight? Enjoy some healthy debate

> in the Yahoo! Answers Food & Drink Q & A.

> http://answers.yahoo.com/dir/?link=list & sid=396545367

>

March 31, 2007

It's not talking about quirkiness, at least from those in AS that I've

talked with. They're talking about curing the gut pain, mercury

toxicity, metabolic problems, seizures, and other biological problems.

> >

> > >

> > > Autism Speaks created a music video of the Five for

> > > Fighting song, " World " ,

> > > which features images of autistic children and their

> > > families.

> > > It is a truly moving video and was the work of Bill

> > > Shea.

> > > The band is generously donating $0.49 to Autism

> > > Speaks for each time the

> > > video is viewed - the funding goes toward research

> > > studies to help find a cure.

> > > When you have a moment, please visit the link below

> > > to watch the video and

> > > pass it along to your friends and family.

> > > They are aiming for 10,000 hits, but hopefully we

> > > can help them to surpass

> > > this goal.

> > >

> > _http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

> > >

> > (http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

> > >

> > > Thanks for your time.

> > >

> > > ************************************** See what's

> > > free at http://www.aol.com.

> > >

> > > [Non-text portions of this message have been

> > > removed]

> > >

> > > [Non-text portions of this message have been

> > > removed]

> > >

> >

>

________________________________________________________________________________\

____

> > Food fight? Enjoy some healthy debate

> > in the Yahoo! Answers Food & Drink Q & A.

> > http://answers.yahoo.com/dir/?link=list & sid=396545367

> >

>

March 31, 2007

It's not talking about quirkiness, at least from those in AS that I've

talked with. They're talking about curing the gut pain, mercury

toxicity, metabolic problems, seizures, and other biological problems.

> >

> > >

> > > Autism Speaks created a music video of the Five for

> > > Fighting song, " World " ,

> > > which features images of autistic children and their

> > > families.

> > > It is a truly moving video and was the work of Bill

> > > Shea.

> > > The band is generously donating $0.49 to Autism

> > > Speaks for each time the

> > > video is viewed - the funding goes toward research

> > > studies to help find a cure.

> > > When you have a moment, please visit the link below

> > > to watch the video and

> > > pass it along to your friends and family.

> > > They are aiming for 10,000 hits, but hopefully we

> > > can help them to surpass

> > > this goal.

> > >

> > _http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

> > >

> > (http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

> > >

> > > Thanks for your time.

> > >

> > > ************************************** See what's

> > > free at http://www.aol.com.

> > >

> > > [Non-text portions of this message have been

> > > removed]

> > >

> > > [Non-text portions of this message have been

> > > removed]

> > >

> >

>

________________________________________________________________________________\

____

> > Food fight? Enjoy some healthy debate

> > in the Yahoo! Answers Food & Drink Q & A.

> > http://answers.yahoo.com/dir/?link=list & sid=396545367

> >

>

March 31, 2007

Right now all they're talking about is genetic

research, unless you talk directly to ,

who is doing her own thing. I don't even particularly

like DAN (we all know that) but they do have some good

to offer...and they aren't sending anyone to their

thing--which is their business but if they're the big

tent of autism they need

a) to really be the big tent of autism

WAY more autistic involvement. They had token input

from a GRASP guy, which was condescending to EVERYONE,

both autistic and NT, that's IT, and one time only.

All their money now is going to genetic research and

big salaries IIRC. It's online. Has to be.

Nothing about seizures, for that you need the epilepsy

societies. For metabolic issues see the appropriate

specialist (mito doc, urea cycle, whatever), et

cetera.

They're going straight for the genes. The last time

someone did that there was a WAR over it. A big world

war.

Kassiane

--- Debi wrote:

> It's not talking about quirkiness, at least from

> those in AS that I've

> talked with. They're talking about curing the gut

> pain, mercury

> toxicity, metabolic problems, seizures, and other

> biological problems.

>

> > >

> > > >

> > > > Autism Speaks created a music video of the

> Five for

> > > > Fighting song, " World " ,

> > > > which features images of autistic children and

> their

> > > > families.

> > > > It is a truly moving video and was the work of

> Bill

> > > > Shea.

> > > > The band is generously donating $0.49 to

> Autism

> > > > Speaks for each time the

> > > > video is viewed - the funding goes toward

> research

> > > > studies to help find a cure.

> > > > When you have a moment, please visit the link

> below

> > > > to watch the video and

> > > > pass it along to your friends and family.

> > > > They are aiming for 10,000 hits, but hopefully

> we

> > > > can help them to surpass

> > > > this goal.

> > > >

> > >

>

_http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

> > > >

> > >

>

(http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

> > > >

> > > > Thanks for your time.

> > > >

> > > > ************************************** See

> what's

> > > > free at http://www.aol.com.

> > > >

> > > > [Non-text portions of this message have been

> > > > removed]

> > > >

> > > > [Non-text portions of this message have been

> > > > removed]

> > > >

> > >

> >

>

________________________________________________________________________________\

____

> > > Food fight? Enjoy some healthy debate

> > > in the Yahoo! Answers Food & Drink Q & A.

> > >

>

http://answers.yahoo.com/dir/?link=list & sid=396545367

> > >

> >

>

________________________________________________________________________________\

____

8:00? 8:25? 8:40? Find a flick in no time

with the Yahoo! Search movie showtime shortcut.

http://tools.search.yahoo.com/shortcuts/#news

March 31, 2007

I guess it's perspective. For example, a lot of DES daughters are

rather resentful that the drug their moms took changed their DNA. I

personally am rather P.Oed that my grandmother's DNA changed after

working on the Manhattan Project. Studying genes isn't *necessarily*

against a person. Learning what changes one's DNA en-utero is trying

to protect the fetus, though many jerks in this world will undoubtably

use it to harm those with genetic changes.

Nope, there's lots of environmental research:

http://www.autismspeaks.com/science/environmental_factors.php

Autism Speaks Grants Related to Potential Environmental Factors in Autism

Autism Speaks is committed to facilitating research that will uncover

the causes of autism, develop effective biomedical treatments, and

hasten the discovery of a cure. As part of this commitment, Autism

Speaks has funded research projects that explore potential

environmental factors in autism. For the years 2005-2007, Autism

Speaks and Cure Autism Now are funding $4,351,716 in grants for

environmental research.

These current grants build on previous commitments by the National

Alliance for Autism Research, or NAAR, and Cure Autism Now. From

1997-2004, NAAR funded $881,984 in grants on environmental factors

(click here for details) while from 2000-2004 Cure Autism Now funded

$748,041 in such research (click here for details). The combined

funding commitment to date on autism environmental sciences is $5,981,741.

Also, learn more about Autism Speaks' current grants for treatment

research.

Current Autism Speaks Grants on Environmental Factors (2005-2007)

Total Funding Commitment: $4,351,716

A. Some examples where toxicant, environmental factor or vaccine

exposure is directly examined (direct part of the research question)

include:

PI: (Mentor-based fellowship, 2005)

Early Markers of Autism and Social-Cognitive Processing in Infants

Exposed to Valproic Acid During Prenatal Development ($54,000)

The use of drugs to control epilepsy (such as valprioc acid) during

pregnancy has been suggested to increase the risk for autism spectrum

disorders in offspring. Thus far, data on autism risk has been based

primarily on case reports, retrospective sample studies, and

suggestions from animal research. This study will assess the

developmental outcomes in a group of infants prenatally exposed to

VPA, as well as a comparison group of infants matched by age, maternal

age and demographic characteristics. It will also examine the effects

of prenatal VPA exposure on motor, mental, and social-emotional

development, as well as social-cognitive processing.

What this means for people with autism: This study will help clarify

if there is indeed an increased risk of autism in children exposed to

valproic acid in utero . Determination of environmental or

pharmaceutical contributions to autism will contribute to development

of better animal models and intervention strategies to prevent VPA

associated cases of autism.

PI: Briscoe (Pilot Award, 2006)

Teratogen-Induced ASD and Brainstem Development. ($59,948)

While the etiology of autism and ASD is unknown, prenatal exposure to

chemical teratogens including the antiseizure medications thalidomide

and valproate are associated with increased incidences of ASD.

Exposure to these agents is known to produce brainstem abnormalities

which are reflected in individuals with autism. While the mechanism by

which these defects are caused by these chemicals is being explored,

the findings do raise the possibility that they may be similar to that

which contributes to autism neuropathology. This project proposes to

initiate a detailed analysis of the effect of thalidomide and

valproate on different species of animals, including the rat, mouse,

chick and zebrafish. The investigators will examine a panel of

molecular markers – genes which will identify specific structures in

the developing brainstem. The identification of chemical induced brain

defects in these organisms will offer the opportunity for many follow

up studies to determine the exact nature of the flaws and how they

cause the symptoms of ASD.

What this means for people with autism: Because exposure to

thalidomide and valproate has been associated with symptoms of autism

spectrum disorder, an understanding of the specific biochemical and

molecular effects of these teratogens during early brainstem

development will help better identify disease mechanism. This

information is likely to have far-reaching implications for

understanding and diagnosing ASD and may aid the development of

therapeutic interventions to treat or ameliorate ASD symptoms.

PI: Croen (Augmentation and Bridge Award, 2006)

Augmentation of CA CADDRE Studies ( $200,000)

Since 2001, the California Center for Autism and Developmental

Disabilities Research and Epidemiology (CA CADDRE) has been one of the

largest, most extensive datasets of information on children with

autism living in California. CA CADDRE, funded by the Centers for

Disease Control and Prevention, is run collaboratively by Dr. Croen

from Kaiser Permanente's Division of Research and Drs. Grether and

Windham from the Department of Health Services. The CA CADDRE center

has also used Kaiser Permanente medical records to investigate autism

risk factors during pregnancy and early childhood.

This grant will fund several new analyses of this rich dataset to

examine risk factors for autism that have been speculated about in the

literature. For example, Dr. Croen and her colleagues will investigate

the risk of autism from:

* prenatal exposure to the immunization RhoGAM, which is given to

women who deliver a Rh+ baby;

* maternal illnesses such as infections, inflammation and

endocrine disorders;

* maternal hormone use, ultrasound exams and maternal use of the

asthma drug terbutaline;

* maternal exposure to environmental chemicals, including airborne

chemicals and workplace exposure.

What this means for people with autism: Data from this study will fill

important gaps in understanding environmental risk factors for autism

spectrum disorders. Researchers will be able to use the results from

these analyses to design future autism studies and, potentially, to

design strategies to prevent autism spectrum disorders

PI: Freedman (Pilot Award, 2004)

Double Hit Hypothesis of Autism: Genetic Susceptibility and

Environmental Exposure to Metals. ($120,000) (Received extension 2005

due to change in investigator to Ed Levin)

High level exposure to the heavy metals mercury and copper can lead to

neuropsychological impairments in adults. Of concern, children are

more susceptible to these cognitive impairments. While the levels at

which exposure has led to dysfunction in motor and memory functions is

considerably high, there are conditions under which an individual can

not properly metabolize/detoxify metals, leading to a high bioburden

compared to exposure level. Drs. Freedman and Levin will test whether

a defect in metal metabolism (genetic) combined with exposure to

copper or mercury (environmental) are causative factors in the

development of autism like behaviors using an animal model. They will

test the hypothesis that a disruption in normal metal metabolism and

concomitant metal intoxication during development contributes to

persistent cognitive and social impairment. Changes in cognitive and

social behavior in response to exposure to copper or inorganic mercury

will be examined in wild type mice and a transgenic strain in which a

central component in metal metabolism, metallothionein, has been

inactivated. The enzyme metallothionein is essential for removing

heavy metals from the body, therefore this genetic manipulation may

serve as a susceptibility factor to the deleterious effects of heavy

metals such as mercury and copper.

What this means for people with autism: The information and improved

mechanistic understanding obtained from the proposed studies will

help define the roles of metal toxicants in the etiology of

neurodevelopmental and neurobehavioral disorders. This information may

be applied to the clinical intervention and possible prevention of

metal-induced neurological disorders.

PI: Hall (CAN Pilot Project Grant, 2007)

Impact of Maternal Infection on Neurodevelopment - Structural and

Functional Changes. ($119,760)

Although autism has a strong genetic component, early exposure to

environmental insult may be a significant risk factor for the

disorder. Exposure to known viruses during the first trimester of

pregnancy has been connected to higher rates of autism. Animal

modeling can be used to directly test if early exposure to immune

challenges causes changes in brain structure, function and behavior

that resemble changes seen in individuals with autism. Dr. Hall is

interested in studying the behavior of mice that have been exposed to

viral infection in-utero. Importantly, he will be assessing the

neurological origins of these behaviors. Using recently available

animal imaging methods he plans to assess the outcomes of maternal

infection upon brain pathways key to autism, focusing especially on

the dopamine and serotonin neurotransmitter systems. These methods

offer the advantage over other techniques that the same animal can be

studied across time. This provides the exciting opportunity to also

study the effects of environmental manipulations on behavioral

outcomes, and connect these results to the neurological changes seen

throughout development. The overall objective of this study is to

localize and quantify molecular events that occur in offspring as a

result of maternal infection. This work holds promise for the

development of new diagnostic tools and improvements in intervention.

PI: Hertz-Piccioto (Augmentation and Bridge Award, 2006)

Bridge Award to the CHARGE study ($25,000)

This study was awarded to Dr. Hertz-Piccioto to bridge NIEHS funding

to her CHARGE study (Childhood Autism Risks from Genetics and the

Environment). The CHARGE study has so far enrolled over 500

participants affected with autism, developmentally delayed, or

not-affected. Her study examines toxicological exposures through

biosampling as well as in depth interviews, monitors medical records

as well as banks biosamples for genetic studies in order to examine

gene-environment interactions.

PI: Hertz-Picciotto (CAN Pilot Project Award, 2006)

Polybrominated Diphenyl Ethers as a Potential Neurodevelopmental

Toxicant ($118,012)

Both genetic and environmental factors contribute to autism in the

majority of cases, yet few specific causes have been identified. In

the search for relevant environmental exposures, chemicals affecting

neurodevelopment are prime suspects. One such group of chemicals is

the polybrominated diphenyl ether (PBDEs). These are flame-retardants

used widely in consumer products, including plastic casings for

television sets and computers, construction materials, carpeting and

foam cushions. Levels of PBDEs are rapidly increasing in the

environment and in human tissues, with body burdens in California

among the highest worldwide. Of foremost concern is the

neurodevelopmental toxicity of PBDEs demonstrated in animal studies.

Prenatal exposures alter spontaneous behaviors, adversely affect

learning and memory, and result in a lack of ability to habituate to a

novel situation. PBDEs cross the placenta, accumulate in the fetus,

and disrupt thyroid hormones, which are crucial for early brain,

motor, language and sensory development. Thus, we will measure PBDEs

in serum collected from children participating in a large

epidemiologic study of autism. The CHARGE (Childhood Autism Risk from

Genetics and the Environment) Study has enrolled over 400 subjects,

including children with autism, children with developmental delay, and

children from the general population. Over 300 of these children gave

blood samples, from which we will select 90 (30 from each group) for

measurement of PBDEs. This project will provide preliminary data to

determine whether children with autism have higher concentrations of

PBDEs than those from the general population or those with

developmental delay but not autism.

PI: Keller (Interdisciplinary Award, 2005)

Comparative Analysis of Cerebellar Neuropathology in Human Autistic

Patients and in Cerebellar Mouse Mutants ($292,02024)

Neuroanatomical and neuroimaging studies in autism conducted by

several research groups show faulty development of neural structures,

particularly in a structure at the base of the brain called the

cerebellum. The cerebellum is a particularly interesting research

target because its structure and function has remained consistent

throughout evolution. In addition, the development of the cerebellum

takes place during late pregnancy and early postnatal life, which is a

period that is believed to be critical for autism. Specifically, the

size of the cerebellum is reported to be smaller in individuals with

autism and the number of cells which direct messages to other brain

areas, Purkinje cells, are shown to be reduced in number.

While the mechanism that affects Purkinje cell number and cerebellar

size is not yet well described, preliminary data suggests that reelin,

an autism candidate gene, interacts with gonadal sex hormones during

cerebellar development. An interaction of abnormal reelin expression

coupled with exposure to differing levels of testosterone during brain

development may contribute to the reduced number of Purkinje cells in

individuals with autism. This study will look for alterations of

enzymes and receptors involved in gonadal steroid signaling in human

brain tissue to determine the interaction between testosterone levels,

reelin expression, and Purkinje cell development. The results of human

brain tissue research will be followed by examining the effects of

estrogen in a genetic strain of mouse named Reeler mice. Reeler mice

lack the reelin protein which leads to a malformed cerebellum with

disorganized Purkinje cells. By using this approach, the effects

changes in gestational environment, including testosterone levels with

genetic mutations on human pathology can be investigated in a

multifaceted way.

What this means for people with autism: This study will investigate

the interaction between genetic vulnerability and gonadal steroid

hormones on Purkinje cell survival, migration, and/or differentiation,

which would account for the biased sex ratio of autism. This

hypothesis has not yet been tested and these researchers will examine

the role of reelin, a candidate gene for autism, and 17beta-Estradiol,

on mouse Purkinje cells. Dr. Keller's group will be linking animal

models with human pathological studies in an interdisciplinary fashion

and studying the possible protective role of estrogen on genetic

susceptibility to autism spectrum disorders.

PI: McCaffrey (Pilot Award, 2005)

Disruption of Organization of the Cerebral Cortex by Retinoic Acid

($119,200)

Summary: Dysfunction of the cerebral cortex is likely to be a

significant contributor to the pathogenesis of autism. One mechanism

by which changes in cortical function may occur is by too much

activity, leading to " overexcitation. " This may be caused by a

dysregulation in systems that normally turn off neurons. In this

study, Dr. McCaffery and associates will investigate the influence of

retinoic acid, which inhibits the migration of specific neurons to the

cortex and so would reduce the number of neurons that regulate brain

activity. Retinoic acid has been suggested as one possible candidate

of an environmental input that, in excess, may result in some features

of autistic pathology. Fetal exposure to retinoic acid can occur

through the use of a number of drugs that can influence the levels or

potency of retinoic acid, including Accutane, alcohol, or valproate.

What this means for people with autism: Studying the effects of

pharmaceutical agents and teratogens on brain development will help

illustrate the mechanisms by which environmental factors may

contribute to the neuropathology of autism.

PI: Newschaffer (Pilot Award, 2005)

Autism, Autoimmunity and the Environment ($120,000)

Summary: There is some evidence regarding an association between

autism and autoimmunity, but the nature of this connection is still

unclear. At the same time, given apparent upsurges in autism

prevalence, interest into environmental risk factors continues to

build. Because autism pathology likely begins early in development,

the prenatal period is a critical time window for exposures to

environmental risk factors. This study will look at two potentially

related factors contributing to the fetal environment: maternal

antibody levels and chemical exposures during pregnancy. The results

of this research will add to the understanding of immunologic and

environmental risk factors in autism.

What this means for people with autism: A reliable biomarker to

enhance diagnosis of autism has not yet been well characterized or

established. This study will explore autoantibodies as potential

biomarkers of autism risk and will link biomarker data with ecologic

data on environmental exposures.

PI: Newschaffer (Pilot Award, 2005)

Autism risk and Exposures/Biomarkers Measured During the pre-, peri-,

and neonatal periods: a Baby Sibs Pilot Investigation ($120,000)

Given the strong evidence supporting the early origins of ASD,

exposure and biomarker data collected during the pre-, peri- and

neonatal time periods could be more strongly associated with ASD risk

because they are measured during an etiologically more significant

time period than those collected later in life. Also, although it is

possible to collect interview data on pre-, peri- and neonatal

exposures retrospectively, prospective collection offers substantive

advantages in reducing error and limiting recall bias.

Collection of biomarker and exposure data in a high-risk cohort offers

some distinct advantages over collecting these data in a

population-based cohort. Most obvious is that, in a high-risk cohort,

informative analyses can be completed with a relatively smaller sample

size because clinical events are more common and there is greater

variation in subclinical (continuously measured) endpoints. A second

advantage of a high-risk cohort is compliance. Motivation to sustain

study participation in the high-risk cohort would likely be higher on

average then in a population-based cohort (although compliance and

sample collection logistics are still a major challenge in this study

design). Finally, studying a genetically susceptible population may

allow for observation of associations between biomarkers and/or risk

factors and ASD that would be more difficult to detect in a

population-based sample.

What this means for people with autism: This investigation will

demonstrate the feasibility of assembling and retaining a study

population to determine if a larger study is possible. The pilot

effort will also focus on data collection areas anticipated to present

particular challenges – for example: the collection of biosamples

during the labor and delivery, post-partum, and early neonatal

periods. Finally, the pilot investigation will provide some data on

the distribution of exposure and biomarker values observed during the

pre-natal period, critical for brain development.

PI: Noble (CAN Pilot Project Grant, 2007)

Cellular, Physiological and Molecular Mechanisms Underlying

Alterations in CNS Development Caused by Exposure to

Clinically-Relevant Levels of Mercury-Containing Compounds ($120,000)

Dr. Noble's research aims to understand the mechanisms by which

genetic factors and environmental insults combine to disrupt normal

brain development and cause complex neurological syndromes such as

autism spectrum disorders (ASD). His laboratory is interested in

understanding how identical insults can have different outcomes in

different individuals. The goal of the research is to provide a

mechanistic understanding of vulnerability to physiological stressors

implicated in ASD. Previous work from the Noble lab has shown that the

state of oxidative stress of individual cells ( " redox state " ) controls

how they react to various environmental agents. The importance of

redox states in controlling multiple cell functions is of potential

interest given the observations that some data suggests individuals

with ASD show signs of being in a more oxidized status. This condition

may make them more vulnerable to physiological stressors. These

studies will focus on thimerosal and methyl mercury in order to

understand the cellular basis for vulnerability to these toxicants,

and are designed to provide general principles relevant to

understanding how any toxicant impinges on normal cell development. As

a part of the proposed research, Dr. Noble aims to uncover approaches

to identifying oxidative stress that could provide the basis for early

identification of children at particular risk of damage from

environmental toxins. They will further apply this knowledge to the

identification of a means to protect such individuals by studying the

efficacy of anti-oxidant compounds in protecting against the cellular

effects of thimerosal and methyl mercury.

PI: Wagner (Pilot Award, 2005)

Animal Model of autism Using Engrailed2 Knockout Mice. ($98,880)

Autism is a neurobiological disorder with primary symptoms include

impaired communication and social interaction with restricted or

repetitive motor movements. Dr. Wagner and his colleagues have

developed a model that examines the neurobehavioral development of

mice in three core areas: motor, cognitive, and social. As the EN2

gene has been shown to be associated with autism, Dr. Wagner's lab

will examine behavioral development in a mouse model where this gene

is not expressed. Furthermore, the effects of two environmental

toxicants, VPA and DEHP will be examined to determine if this gene

confers susceptibility to environmental exposures. He predicts that

disruption of the En2 gene will alter the developmental path of the

brain and lead to widespread behavioral changes that may be made worse

in the presence of these toxicants.

What this means for people with autism: These studies may help clarify

the genetic, neurobiological and environmental influences in autism.

Finding genes involved in autism susceptibility and learning how they

contribute to disease development will provide information that could

lead to more effective treatments and interventions.

B. Other studies which indirectly examine toxicant exposure/immune

function:

PI: Ashwood (CAN Pilot Project Award, 2006)

Immunological Phenotyping in Autism: A Screen for Potential Early

Biomarkers of Activation ($120,000)

It is thought that the interaction of genetic susceptibility and

exposure to nongenetic influences during critical periods of

neurodevelopment plays a part in the development of autism. Virtually

the entire research literature on autism emphasizes the multiple

facets of this disorder. Taken together, these data indicate that ASD

is, in reality, a group of disorders that share a common behavioral

profile. To make progress in identifying the causes of these disorders

it will be essential to develop diagnostic markers that will lead to

unequivocal differentiation of the various phenotypes. We aim to

demonstrate the presence of distinct immune phenotypes in ASD based on

the level of activation of their immune response. We will identify and

characterize the immune response in ASD by comparing the activation

status and function of lymphocyte cell populations and their

cytokine/chemokine profiles, firstly in peripheral blood and secondly

in isolated cell cultures that receive immunological challenge.

Immunological findings will be correlated with behavioral and

biomedical factors to examine the relationship between the immune

responses and clinical characteristics of autism. By elucidating the

medical and biological correlates of autism, we hope to contribute to

a clearer understanding of the early biological processes underlying

this increasingly common disorder. A better understanding of the

underlying biology may contribute to earlier identification and the

development of more individual-based treatment regimens.

PI: Boulanger (Mentor-based Fellowship, 2006)

Modulation of Glutamate Receptor Trafficking in Autism: Role of MHC

class I ($84,000)

There is growing evidence of an imbalance in neuronal signaling in the

brains of some individuals with autism. The neurotransmitter glutamate

is an important chemical that " turns on " neurons. Direct measures of

glutamate neurotransmission have been used to measure proper neuronal

signaling in animal models. Recent studies have linked the ability of

neurons to respond to the neurochemical glutamate to the changes in

immune response. Because maternal immune challenge during pregnancy

may be a risk factor for autism in children, this raises the

possibility that maternal immune challenge may alter glutamatergic

neurotransmission. This is may be accomplished through modification of

MHC class I molecules (major histocompatibility complex class I) in

the developing fetal brain. MHC-I molecules are an essential part of

the immune response which are now known to be expressed in the brain

and modulate neuronal function.

Using a mouse model, Drs. Boulanger and Fourgeaud will test whether

changes in MHC class I in the developing brain effects glutamate

receptors, and whether these changes can be induced in the fetal brain

by maternal immune challenge. Together with the projects mentored by

Dr. McAllister and Dr. , the role of alterations in immune

function on brain development and later behavioral function will be

better understood.

What this means for people with autism: These studies could also

provide a mechanistic link between maternal immune challenge, a

significant environmental risk factor for autism, and glutamatergic

dysfunction, a hallmark symptom of this disorder. Furthermore, the

results of these studies may suggest new, immune-based strategies for

the diagnosis, treatment, and prevention of autism.

PI: Boulanger (CAN Pilot Project Award, 2006)

Immune Genes and Abnormal Brain Development in Autism ($120,000)

In this study Dr. Boulanger outlines the connections between autism

and immunological challenges. She will study how a variety of material

infections, such as influenza, may affect the development and behavior

of the fetus, even when the fetus shows no signs of direct infection

itself. The fetal impact appears to be the result of a relatively

nonspecific aspect of the maternal immune response, but is reflected

in altered cytokines in the fetal brain. This study will use mouse

models and autistic children to explore whether the expression of

immune genes is altered in the autistic brain, perhaps highlighting

the potential for immune-based diagnostics, treatment and prevention.

PI: Deth (CAN Pilot Project Award, 2006)

Glutathione-dependent Synthesis of Methylcobalamin: A Target for

Neurodevelopmental Toxins ($117,880)

While the exact cause of autism is not yet known, research during the

past several years has focused on the possibility that many cases of

autism result from exposure to the ethylmercury-containing vaccine

preservative thimerosal. A subgroup of exposed individuals may be less

able to detoxify and eliminate heavy metals, placing them at higher

risk. Previous work from our lab has shown that thimerosal and other

heavy metals potently inhibit an enzyme that uses vitamin B12, and

that this inhibition could lead to developmental disorders like

autism. Thimerosal interferes with the process that converts dietary

B12 to its active form, known as methylB12. MethylB12 has proven to be

quite helpful in treating autism, which reinforces the idea that

impaired methyl B12 synthesis may be an important contributing cause.

Thus this project will investigate the biochemical pathway that makes

methylB12 and will elucidate the mechanism by which thimerosal causes

its inhibition. It will also compare the thimerosal susceptibility of

this pathway in cells from siblings who did or did not develop autism.

Preliminary results suggest that the autistic children's cells show

greater sensitivity. Results from this study will help to clarify what

causes autism and what makes one child more likely to develop autism

than another.

PI: Holtzman (CAN Pilot Award, 2007)

Oxidative Phosphorylation in Cells from Autistic Individuals Compared

to Non-Autistic Siblings ($120,000)

This study analyzes whether metabolic abnormalities contribute

directly to the pathogenesis of autism. Using patient cell lines, the

project is designed to identify any abnormalities in mitochondria and

the generation of ATP, the chemical form of energy. If successful,

these results will lead directly to studies of the genetic mutations

or toxic reactions important in the development of autism.

PI: Jonakait (CAN Pilot Project Award, 2006)

Microglial Regulation of Cholinergic Development in the Basal

Forebrain ($112,778)

While the neurobiological basis for autism remains poorly understood,

neuropathological studies have detected structural abnormalities in

certain brain regions suggesting that disruption of normal brain

development may play a role in the disorder. Our work highlights one

of those abnormal brain regions, the so-called cholinergic basal

forebrain, that innervates important brain areas serving cognitive

function. Autistic children have too many neurons in this region, but

how such changes might occur in development has not been explained.

Increasing evidence also suggests that fetal exposure to infectious

agents or toxins with associated inflammation may play a role in the

development of autism. Such infection or toxicity can extend to the

embryonic brain where local inflammation might prove detrimental to

the developing brain. Our own work performed on cultured rodent cells

suggests that abnormal embryonic brain inflammation during development

leads directly to abnormal neurodevelopmental outcomes. Specifically,

it leads to the excess production of cholinergic neurons in the basal

forebrain. Thus, we have shown directly that brain inflammation has

important neurodevelopmental consequences. Our proposal seeks to

extend those studies by investigating in vivo whether maternal

infection will lead to a similar excess of cholinergic neurons in the

fetal brain. We will also seek to determine whether several known

inflammatory signals will act similarly in culture and what

developmental mechanisms they might use to create excess numbers of

these neurons. Finally, we hope to begin to identify the specific

molecules that cause the basal forebrain to develop abnormally.

PI: Kawikova (Pilot Award, 2006)

Does Autoimmunity play a Role in the Pathogenesis of Autism ($120,000)

Many neuropathological studies in autism have reported a reduction in

numbers of cells in the brain in areas which control motor

coordination and cognitive functioning. While the mechanism of this

loss in cell number is unknown, a recent study demonstrated the

presence of inflammation in the same brain areas. This suggests that

an autoimmune process may play a role in the neuronal loss observed in

autism. Autoimmunity occurs when the immune system not only protects

the body against infectious microorganisms, but mounts an immune

response against one's own tissue. This experiment will investigate

whether the mechanisms which regulate autoimmunity are inadequate in

children with autism and whether this is accompanied by signs of

immune system activation. Measures of immune function will also be

coupled with diagnostic instruments to shed light on whether changes

in immune system activation is related to the severity of autism

symptoms which is different from individual to individual.

PI: Le Belle (CAN Pilot Project Award, 2006)

Molecular and Environmental Influences on Autism Pathophysiology (CAN

Young Investigator Award, 2006; $80,000)

The incidence of macrocephaly (enlarged head) in the population of

autistic patients is considerably higher than in control populations

and indicates that this may contribute to the development of ASD. We

are interested in what genetic and environmental changes underlie the

development of macrocephaly and autism. Mutations in PTEN can be found

in some autistic patients with macrocephaly. We have a mouse model of

macrocephaly in which the gene PTEN has been deleted, resulting in the

abnormal growth of brain cells, producing animals with large heads. We

have recently shown that PTEN has a role in the ability of normal

brain stem cells to self-renew, proliferate, and grow. We will use a

relatively new technology in the study of gene expression in the

brain, called microarray, to identify genes that are changed in our

macrocephalic PTEN mutant mice. These experiments may identify genes

and gene networks that contribute to ASD. We will also study how PTEN

activity is affected by environmental factors. One such factor is

oxidative stress. Oxidative stress is a general term used to describe

oxidative damage to a cell, tissue, or organ, caused by reactive

oxygen species. Most reactive oxygen species come from the internal

sources as byproducts of normal cellular metabolism, such as energy

generation from mitochondria. External sources include exposure to

cigarette smoke, environmental pollutants such as emission from

automobiles and industries, consumption of alcohol in excess,

asbestos, exposure to ionizing radiation, and bacterial, fungal or

viral infections. We and others have found that low levels of

oxidative stress can enhance the self-renewal and proliferation of

brain stem cells when grown in a culture dish, and this also results

in decreased amounts of PTEN gene expression. We propose to look

further at this potential mechanism by over-expressing pro-oxidant

genes and disrupting anti-oxidant genes in cultured cells and in

developing mouse embryos to determine if oxidative stress is a key

environmental factor in the development of ASD with macrocephaly.

PI: Lipkin (CAN Pilot Project Award, 2006)

Histologic, Microbiological and Molecular Analyses of Bowel Disease in

ASDs ($120,000)

Debilitating gastrointestinal (GI) dysfunction is described in some

autistic children, possibly at higher frequency in individuals with a

regressive phenotype. Its cause is unknown; however, some studies have

implicated inflammation or infection. The significance of

gastrointestinal dysfunction for brain dysfunction is controversial;

some investigators have proposed that differences in GI microflora

induce inflammation, influence permeability of the GI tract, or

release novel neuroactive peptides that have remote effects in brain.

Our project will use sensitive new assays for gene expression,

microbiology and immunology to survey GI tract biopsies and blood from

two groups of children: one group with GI dysfunction and autism, and

one group with GI dysfunction but no neurological disturbance. The

implication of an infectious agent (or agents) as factors (or

cofactors) in autism or associated GI comorbidity could lead to new

strategies for prophylaxis or therapeutic intervention. Discovery of

distinct profiles of gene expression in GI tract or of soluble factors

in peripheral blood may provide insights into pathogenesis; inform

genetic analyses; and facilitate management by providing therapeutic

targets and objective criteria for diagnosis and treatment response.

PI: McAllister (Mentor-based Fellowship, 2006)

The role of MHC class I molecules in synapse formation: possible

implications for the pathogenesis of autism ($78,000)

Although there is a strong genetic component to autism and autism

spectrum disorder, there are non-genetic causal factors. Maternal

viral infection has been put forward as one such factor. During an

infection, the immune system releases molecules called cytokines which

then trigger an increase in MHC-I molecules. Dr MacAllister's team has

previously shown that altered MHC-I levels can affect the brain by

reducing the ability of neurons to form synapses and modifying

existing connections. Therefore, it is possible that modifications of

immune function may alter normal brain development and possibly

produce symptoms of ASD.

This new research will investigate the specific role of cytokines on

MHC-I expression and how these changes affect neuronal development.

This will be done by measuring MHC-I levels after administration of

cytokines as well as examining the number of synapses following

exposure. Finally, the function of these neuronal connections will be

tested to determine whether the immune response, possibly altered in

autism, leads to impaired connectivity and circuitry.

What this means for people with autism: Changes in immune system

function have been reported in individuals with autism, but the

consequences of this hyperactivity on brain development are not yet

well understood. These studies will lead to a better understanding of

the neurobiological consequences of altered immune activity, and how

they relate to ASD.

PI: McAllister (CAN Pilot Project Award, 2006)

A Role for Immune Proteins in Early Stages of Neural Development:

Possible Implications for the Pathogenesis of Autism (CAN Pilot

Project Award, 2006; $120,000)

Proper formation of connections in the brain during childhood provides

the substrate for adult perception, learning, memory, and cognition.

Tragically, improper formation or function of these connections leads

to many neurodevelopmental disorders, including autism. Autism

spectrum disorder is a highly prevalent severe neurobehavioral

syndrome with a heterogeneous phenotype. Although there is a strong

genetic component to autism, the syndrome can also be caused or

influenced by nongenetic factors. Specifically, maternal viral

infection has been identified as the principle nongenetic cause of

autism. Several studies have even indicated a genetic link between

autism and immune system genes. Since immune molecules are increased

following infection and are present in the developing brain, it is

possible that changes in these immune molecules lead to changes in

neuronal connectivity that underlie some forms of autism. This

proposal will test this idea by studying the function of altered

levels of a specific kind of immune molecule on the initial formation

of connections and their subsequent plasticity in the developing

brain. Thus, our results should reveal a mechanism for the primary

nongenetic cause of autism and thereby illuminate potential preventive

therapies for this devastating disease.

What this means for people with autism: Determining the precise role

of specific immune activity may elucidate an important immune

mechanism leading to inflammation in CNS of autistic patients, as well

as open new therapeutic possibilities for these patients.

PI: Pessah(CAN Environmental Initiative Innovator Award, 2006)

Contribution of Calcium Channel Mutations to Autism Risk and Mercury

Susceptibility ($140,000)

The goal of this research is to understand the genetic and

environmental risk factors contributing to the incidence and severity

of core symptoms and comorbidity seen in childhood autism. Dr. Pessah

hypothesizes that mutations in specific types of calcium (Ca2+)

channels may contribute to certain forms of autism and significantly

increased susceptibility to adverse effects of environmental

toxicants. This hypothesis is based on evidence from the Pessah lab

that organic mercury, polychlorinated biphenyls, and flame retardants

(PBDEs) can alter the intracellular Ca2+ signals generated by

ryanodine receptors, an important type of calcium channel, and that

these receptors are essential for normal maturation and function of

both the immune and nervous systems. To attain these goals, mice that

contain mutations for calcium channels will be studied for abnormal

social behavior and their possible heightened susceptibility to

organic mercury compounds such as thimerosal will be studied in

detail. One mouse currently being developed possesses a mutation

within a specific calcium channel (Cavl.2) that has been found to

cause Syndrome (TS). Children with TS have a 60% rate of an

autism diagnosis, with up to 80% of the children showing some signs of

autism. Two additional mouse models are currently being studied that

possess a mutation within the type 1 or type 2 ryanodine receptor Ca2+

channel (RyR1 and RyR2, respectively). Dr. Pessah's lab has found that

mice possessing mutations in RyR channels have heightened

susceptibility to chemically-induced adverse reactions of the immune

and nervous systems. Together, the Cavl.2 and RyR2 receptors form a

signaling unit in heart, neurons and T lymphocytes. This project will

investigate whether these three lines of mice, which have an

underlying genetic defect in Ca2+ signaling, will have increased

behavioral and immunological problems when exposed to mercury, and

will also examine whether mercury directly affects the development of

nerve cells from these animals. Finally, the Pessah lab will determine

whether children with autism have a higher frequency of Cavl.2 or RyR

mutations. Collectively these experiments will provide important new

information on the possible contribution of Cavl.2 or RyR mutations to

autism risk in humans and launch studies of enhanced susceptibility of

the developing nervous and immune systems to organic forms of mercury

in mice carrying mutations relevant to autism.

PI: Rosenspire (CAN Pilot Award, 2007)

The Overlap Between Celiac Disease and Autism - Potential Inflammatory

Responses Exacerabated by Exposure to Toxicants Such as Mercury ($60,000)

The aim of this grant is to research the connection between autism and

celiac disease (CD), an autoimmune disorder of the small intestine

characterized by intolerance to dietary gluten. Establishing an

unambiguous link of CD to autism will allow them to pursue their

hypothesis that CD may lead to inappropriate inflammation in the

brain, and that patients with CD may also be especially prone to

adverse inflammatory responses upon exposure to environmental

toxicants such as mercury.

PI: Silbergeld (CAN Pilot Project Award, 2006)

Genetic Susceptibility to Mercury-induced Immune Dysfunction in Autism

and Autism- Spectrum Disorders ($120,000)

The goal of this project is to examine genes that may affect responses

to environmental risk factors in autism and autism spectrum disorders

(ASD). These are complex diseases that are known to involve

interactions between genetic susceptibility and acquired (or

environmental) exposures. However, most research on autism/ASD

development has not examined these interactions, but rather focused on

either genetic or environmental risk factors, including mercury

compounds. The failure to include gene-environment interactions may be

one reason why we have not yet identified either key genes or

significant environmental risk factors associated with autism/ASD. We

plan to examine whether there are differences in how children with

autism/ASD respond to one environmental contaminant (mercury) compared

to their unaffected siblings and parents. We hypothesize that mercury

does not cause autism by itself, but that individuals who carry

certain variations in specific genes may have heightened responses to

mercury, and that these variations will increase the likelihood that

those children exposed to mercury will develop autism/ASD. In order to

accomplish our goal, we will first develop and validate a panel of

tests using immune cells found in human blood to quantitate immune

responses to mercury in vitro by using the blood of healthy

volunteers. Then we will apply this panel to cells obtained from

children diagnosed with autism/ASD, their unaffected siblings, their

parents, and unrelated community controls. This project will be the

first study on this topic conducted in cells from human subjects.

Eventually, we hope to identify variations in specific genes related

to these responses to mercury for use in epidemiological studies of

autism/ASD.

PI: Singer (Pilot Award, 2005)

Autoimmune Abnormalities in Autism: a Family Study ($120,000)

Several theories have been proposed based on the presence of

antineurononal antibodies (ANAb) in individuals with autism. One study

suggests that autism may be caused by the placental transfer of

antibodies that, in turn, interfere with the development of the fetal

brain. A second hypothesis suggests that identifying antibodies

against specific central nervous system (CNS) proteins is essential in

providing clues about the underlying pathophysiology. In order to

further investigate the possibility of placental transfer of

antibodies as a cause for autism, Dr. Singer's research will compare

antibody levels in mothers of children with autism to those of

unaffected children. He will also study both adult and fetal

postmortem brain tissue to look at differentiation based on

developmental factors.

What this means for people with autism: The identification of

autoimmune abnormalities can aid in the definition of the autism

phenotype, and provide new insight for physiological mechanisms behind

the cause of autism as well as potential preventative therapy.

PI: Wills-Karp, Malloy, Manning- (Pilot Award, 2006)

Does Immune System Dysfunction Play a Role in Autism? ($100,000)

Recent evidence suggests that the immune system, which normally

protects the body against many diseases, may malfunction in people

with autism and actually contribute to or produce this disorder.

" Adaptive " immune " T " cells are summoned by `innate " immune cells to

attack invaders. Immune T cells in some people, however, mistake the

body's own tissues as foreign and attack them, a process called

" autoimmunity. " Immune T cells also can over-react to otherwise

harmless substances, such as pollen, and produce allergies. Usually

these potentially errant responses by immune T cells are kept under

control by `regulatory T cells. " Regulatory T cells are produced by

the Foxp3 gene. According to the collaborating researchers, who

combine expertise in autism, immunity, and patterns of disease

( " epidemiology " ), a disproportionate number of children with autism

have immune system malfunctions that are similar to those seen in

autoimmunity, allergy, or both conditions. They hypothesize that

regulatory T cells in people with autism may be too few, or too weak,

to provide a generalized ability to control errant immune responses,

which contributes to, or causes, autism.

The collaborators will study immune T cells, which circulate through

the bloodstream, in blood samples taken from 20 children with autism

and 20 healthy ( " control " ) children. They will compare the number of

regulatory T cells, and how effectively these cells control the

" attacker " T cells, in blood samples from the two groups of children.

The investigators also will find out whether differences exist in the

two groups of blood samples in the amount of chemicals, called

`cytokines, " produced by attacking T cells. Excessive amounts of these

cytokines, suggesting incomplete control of T cells by their

regulators, may have consequences for the brain, providing a link

between immune dysfunction and autism. Alternatively, some other

factor may be common to both immune regulation and to autism.

What this means for people with autism: If this study indicates that a

failure to properly regulate immune T cells is involved in autism, the

research will provide a better understanding of immune system

involvement in autism. The findings also may provide an immune

" marker " to diagnose autism, and lead to development of specific

immune-based therapies to prevent or treat autism.

PI: Vogel (Pilot Award, 2006)

Neuroinflammation, the Kynurenine Pathway, and Autism($118, 692)

Although the causes of autism are still unknown, there is growing

evidence that genetic, environmental, and immunological factors may

contribute to the development of the disorder. Many cases of autism

are reported to be associated with chronic activation of the immune

system. This experiment will investigate markers of chronic

neuroinflammation in brain tissue from individuals affected with

autism. These markers will be compared to levels of two newly studied

neuroactive compounds which have been associated with cell death:

kynurenic acid (KYNA) and quinolinic acid (QUIN). Dr. Vogel and his

colleagues will investigate if alterations in the relative abundance

of KYNA and/or QUIN affect the development and functioning of neural

circuits or induce damage in the nervous system thereby contributing

to the development of autism.

What this means for people with autism: Alterations in immune system

function has been associated with autism, however, the link between

immune reactivity and onset of autism spectrum disorder has not been

clearly defined. Changes in KYNA and QUIN in human postmortem tissue

along with other neuropathological alterations would help better

define the relationship of the immune system in brain development and

neurodevelopmental disorders. These results could lead to new targets,

possibly those in the immune system, for the development of novel

treatments for autism.

PI: Vogt (Pilot Award, 2005)

Immune Biomarkers in Serum and Newborn Dried Blood Spots ($118,880)

At present, there are no biological tests that can be performed to

diagnose autism. This study will help develop methods and establish

reference ranges for measuring immune biomarkers in infants, children,

and mothers that could aid in early recognition and diagnosis of

autism. The researchers will investigate if autism may be caused by

immune and inflammatory reactions that influence neural development

during gestation and infancy. They will use the microbead suspension

array (MSA), which is a flexible, highly sensitive assay system that

can be used to measure multiple biomarkers simultaneously from a very

small sample, such as a drop of blood. Dr. Vogt and his colleagues

hope to develop a panel of reliable, transferable laboratory methods

for measuring selected biological markers of the immune system in

serum and dried blood spots (DBS).

What this means for people with autism: This study will help establish

tests and reference ranges that are readily transferable to other

laboratories, so that all research and public health investigators can

make use of them. Ideally, these population- based research activities

will implicate specific environmental triggers of autism and help lead

to preventive measures.

C. Studies which investigates other environmental factors:

PI: Chen (Pilot Award, 2006)

Testing the " Extreme Male Brain " Theory of Autism ($100,000)

Autism occurs four times more frequently in males compared to females,

suggesting that a complex genetic predisposition, involving hormones,

is involved. According to these researchers, since females have

stronger emphasizing capability, while males have stronger systemizing

capability, an " extreme male brain " (EMB) theory may explain the

genetic basis of autism. This theory proposes that individuals along

the autism spectrum are characterized by impairments in empathy

alongside intact or even exceptional systematizing capacities. The

researchers suggest that endogenous hormone levels of either or both

the parent and the fetus during development are important. They

hypothesize that inherited genetic variations in androgen metabolism

modify the risk of autism, that there is a critical time when fetal

exposure to androgens, specifically testosterone, is related to later

development of autism spectrum disorder.

They will test the EMB theory by undertaking genetic studies in 260

mother-child pairs in which the child has autism. First, the

researchers will identify different forms of androgen-metabolizing

genes that are biomarkers for integrated hormone levels. They then

will assess this relationship between androgen metabolism and autism

risk by analyzing forms of genes that favor the production and

accumulation of testosterone. Thereafter, they will confirm whether

the forms of genes identified occur in 300 healthy mother-child pairs,

and whether maternal or fetal hormonal levels are key. Through this

process, the researchers will derive direct evidence on whether or not

the EMB theory is valid.

What this means for people with autism: If the EMB theory is

validated, it would lead to further clinical efforts to assess genetic

or individual susceptibility factors that increase the risk of autism,

and to explore whether contributing hormonal, environmental or dietary

exposures might be minimized.

PI: Dodds (CAN Pilot Project Award, 2007)

Risk for Developing Autism: A Population-Based Longitudinal Study of

Obstetric and Neonatal Factors ($119,662)

Autism is part of a spectrum of disorders that are characterized by

severe impairment in social interaction and communication and by the

presence of inflexible behavior. Numerous reports suggest a trend of

increasing rates of autism in Canada and in other countries, although

it is not clear whether this increase reflects increased awareness of

autism and changes in the way autism is diagnosed or whether the

increase reflects true population increases in the disorder. Little is

known about the causes of this disorder. Several recent studies have

suggested that problems in pregnancy or in the newborn period may play

a role in the development of autism. The purpose of this study is to

use a population-based approach to identify pregnancy and newborn

factors that are associated with the subsequent development of autism.

Understanding the role of early life factors that are related to the

development of autism is a first step towards early diagnosis and

intervention.

PI: Happe (Mentor-based Fellowship, 2006)

From Genes to Behavior: A Multidisciplinary Investigation of the

Autism Triad ($82,000)

Most research on autism spectrum disorders (ASDs) has assumed that the

three core behaviors that represent ASDs—social impairments,

communication, and restricted/repetitive behaviors – the " triad " are

interrelated. However, it is possible that these three domains may be

very different and caused by different mechanisms. This implies that

different features of autism may be caused by different genes,

associated with different brain regions and related to different core

cognitive impairments. Dr. Happe and her colleagues, therefore propose

that research is likely to learn more about ASDs by examining each of

these behaviors separately.

Dr. , the post-doctoral fellow, will conduct new

analyses to examine individual differences in affected and

non-affected people in three domains of cognitive processing. She will

also identify genetic markers and environmental factors which are

associated with each core behavior. This will help better identify the

causes for each symptom of autism, and determine if they can be

separated from one another. Data and resources from the Twins Early

Development Study, will be used to expedite findings. The

post-doctoral fellow is well qualified for this project, having

already published several papers on autism research and recently

received the 2006 Young Investigator Award by the International

Society for Autism Research.

What this means for people with autism: This research will take a

novel approach to studying the gene-brain-behavior pathways in ASDs by

examining the three core behavioral traits of ASD separately. If the

theory holds up and different features of autism are caused by

different genes, associated with different brain regions, and related

to different core cognitive impairments, the findings from this study

may lead to tailored interventions designed to address specific

characteristics of each behavioral trait.

PI: Kinney (CAN Pilot Project Award, 2005)

Do Environmental Factors Play a Role in Autism? A Test Using Natural

Experiments ($80,000)

Whether environmental factors play an important role in causing autism

is a crucial - and hotly debated - question. Many studies report

unusually high rates of medical problems during the gestations and

births of persons who later developed autism, suggesting that

environmental factors occurring before or around the time of birth may

contribute to the development of the disorder. Skeptics, however,

argue that the same genes that cause autism also cause these high

rates of pregnancy and birth complications. The most powerful

scientific approach to deciding this issue -- an experiment in which

pregnant women were randomly assigned to low vs. high stress

conditions - would clearly be unethical. We use an alternative

strategy that uses natural disasters as " experiments of nature " to

test the hypothesis that exposure to stressful events during

vulnerable weeks of gestation significantly increases risk of

developing autism. Anonymous data on more than 4,000 persons with

autism from three different states, as well as on 2 million general

population births in these same states, will be studied to investigate

whether autism rates are significantly increased among individuals who

were in certain weeks of gestation at the time their mothers were

exposed to natural disasters such as extremely destructive

earthquakes, hurricanes, and severe blizzards. Confirmation that pre-

and perinatal environmental stressors play a significant role in

causing autism would have important implications for the treatment and

prevention of autism.

PI: Nair (Special Project, 2006)

Neurodevelopmental disabilities among children in India($100,000)

Given current epidemiologic estimates, there are approximately 1.7

million individuals with autism in India. The primary objective of

this research project is to assess the screening and diagnostic

prevalence of neurodevelopmental disorders, including autism, in

children between the ages of 2-9 in India and gain information on risk

factors in these children. The investigators will develop a novel

neurodevelopmental disability screening tool and consensus clinical

criteria, and validate these instruments so that they can be used in

as a diagnostic instrument for further evaluation of the prevalence of

autism in this country. In addition to studying the prevalence of

autism in Indian, the investigators will also identify the full

clinical spectrum of autism using their test instruments. In addition

to case ascertainment, potential risk factors for autism, including

infections, nutritional deficiencies and genetic factors will be

identified through open ended interviews with health personnel.

What this means for people with autism: The identification of an

initial nation-wide developmental disability cohort would allow more

refined characterization of the Indian autistic population, setting

the stage for exploring future scientific opportunities in causes

(more comprehensive epidemiology and genetic studies), diagnosis (Baby

Sibs), and treatment (clinical trials) in that country. By generating

valid data from India, capturing socio-cultural and geographical

variability, researchers can better identify the true worldwide

prevalence of autism and further quantify risk factors which may

contribute to these differences.

PI: (Mentor-based Fellowship, 2006)

Role of Cytokines in Mediating the Role of Maternal Immune Activation

in the Fetal Brain ($52,000)

Children whose mothers develop infections during pregnancy are at

increased risk for autism, schizophrenia or other neurodevelopmental

disorders. However the molecular pathway that leads from infection to

autism is unclear. Using an animal model of maternal viral infection,

Dr. have shown that the maternal immune reaction, rather

than the virus itself, interferes with fetal development leading to

behavioral symptoms of heightened anxiety and decreased social

interaction.

This experiment will establish which specific immune factors interfere

with fetal brain development. Four different immune factors will be

tested to produce and then reverse early behavioral deficits in

offspring exposed in utero to these immune factors. Any immune factor

that meets both criteria will be a leading candidate for continued

research into specific molecular pathways that interfere with normal

development and lead to autism-like symptoms.

What this means for people with autism: This project will use a mouse

model of a known risk factor for autism—maternal viral infection—to

determine a mechanism that elicits changes in fetal brain development

and leads to the autistic phenotype. These findings could lead to a

better understanding of what goes wrong in autism, and suggest

potential methods of preventing the disorder.

PI: Rakic (Mentor-based Fellowship, 2006)

Effects of a Non-Steroidal Anti-Inflammatory Drug on Neuronal

Migration ($101,000)

While the precise causes of autism is not yet known, multiple genetic

and environmental factors are thought to play an important impact on

the development of the disorder. The site where certain neurons

connect, called gap junctions, are sensitive to environmental agents

and have downstream effects on cell growth and reproduction, and

possibly on migration of neuronal precursors to their appropriate

destinations. In order to manipulate the function of the gap junction

in an animal model, the investigators will test the effects of an

NSAID which alters the function of gap junctions on the activity of

neurons during development and migration. Deficits in neuronal

migration and formation of different layers of the cortex may lead to

the neuropathological and behavioral features observed by other

scientists.

The mentor and the fellow will use advanced molecular biology

techniques to trace the position of the migrated neurons during

critical periods of neuronal development. They will also study

properties of the misplaced neurons to determine their abilities to

participate in a functional network. Finally, behavioral analysis of

offspring exposed to prenatal NSAIDS will be performed. This will help

better link any neurobiological differences with functional outcomes,

especially as they relate to the symptoms of autism spectrum disorder.

What this means for people with autism: Using disruption of the gap

junction by biophysical and environmental factors will help identify

the cause of cortical malformation. This will be relevant to a better

understanding of brain development as well as the causes of autism

spectrum disorders

PI: Schmitz (Pilot Award, 2005)

Cytoarchitectural Alterations in the Cerebral Cortex in Autism($120,000)

Dr. Schmitz's lab has been studying the neuropathological

characteristics of autism for many years. His group has reported

abnormalities in size, number, and organization of neurons in the

cerebral cortex. This current study will utilize novel tools to view

the organization of cells in the cortex in three dimensions,

specifically examining the connectivity of neurons between different

areas of the cortex. Furthermore, his lab will compare these changes

with those of a current animal model of autism: in utero maternal

influenza virus exposure.

What this means for people with autism: The results of the proposed

project will contribute to a better understanding of the

neuropathology of autism using software which will be made available

to the research community. In addition, this study will investigate

the validity of an animal model of autism where environmental factors

play a key role.

PI: Windham (Pilot Award, 2006)

Autism and Prenatal Hormone Markers($60,000)

The California Department of Health Services is currently tracking the

prevalence and demographic characteristics of autism. This data will

be linked to hormone and protein markers measured during pregnancy.

This is made possible though the California prenatal screening

program, in which several hormones or protein markers were measured in

maternal blood during the second trimester. In the proposed study, the

levels of these hormone/protein in nearly 2,000 pregnant women and

their offspring who are later diagnosed with autism, compared to the

nearly 600,000 screened births during the same two years. Although

hormonal factors have been frequently suggested as contributing to the

occurrence or severity of autism, few studies have investigated this

hypothesis.

What this means for people with autism: The results will help shape

further research to rigorously evaluate complex interactions between

genetic factors, in utero hormonal factors, and environmental factors

in relation to autism. In addition to the analyses proposed, the

investigators have numerous opportunities for follow-up, including

examining similar parameters in other birth years, examining other

newborn screening markers, and potentially obtaining newborn blood

spots for genotyping. The proposed study provides a unique and

cost-effective opportunity explore important data on a very large

population.

> > > >

> > > > >

> > > > > Autism Speaks created a music video of the

> > Five for

> > > > > Fighting song, " World " ,

> > > > > which features images of autistic children and

> > their

> > > > > families.

> > > > > It is a truly moving video and was the work of

> > Bill

> > > > > Shea.

> > > > > The band is generously donating $0.49 to

> > Autism

> > > > > Speaks for each time the

> > > > > video is viewed - the funding goes toward

> > research

> > > > > studies to help find a cure.

> > > > > When you have a moment, please visit the link

> > below

> > > > > to watch the video and

> > > > > pass it along to your friends and family.

> > > > > They are aiming for 10,000 hits, but hopefully

> > we

> > > > > can help them to surpass

> > > > > this goal.

> > > > >

> > > >

> >

> _http://www.whatkindofworlddoyouwant.com/videos/view/id/213154_

> > > > >

> > > >

> >

> (http://www.whatkindofworlddoyouwant.com/videos/view/id/213154)

> > > > >

> > > > > Thanks for your time.

> > > > >

> > > > > ************************************** See

> > what's

> > > > > free at http://www.aol.com.

> > > > >

> > > > > [Non-text portions of this message have been

> > > > > removed]

> > > > >

> > > > > [Non-text portions of this message have been

> > > > > removed]

> > > > >

> > > >

> > >

> >

>

________________________________________________________________________________\

____

> > > > Food fight? Enjoy some healthy debate

> > > > in the Yahoo! Answers Food & Drink Q & A.

> > > >

> >

> http://answers.yahoo.com/dir/?link=list & sid=396545367

> > > >

> > >

> >

>

________________________________________________________________________________\

____

> 8:00? 8:25? 8:40? Find a flick in no time

> with the Yahoo! Search movie showtime shortcut.

> http://tools.search.yahoo.com/shortcuts/#news

>

March 31, 2007