FW: Errant Protein Could Solve Riddle Of Autism/ Autism on the Rise

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Errant Protein Could Solve Riddle Of Autism/ Autism on the Rise

FEAT DAILY NEWSLETTER Sacramento, California http://www.feat.org

" Healing Autism: No Finer a Cause on the Planet "

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May 10, 2001 Search www.feat.org/search/news.asp

BREAKING NEWS - Another Significant Medical Finding

Also: * New Research Suggests Cause of Autism

* Autism on the Rise: The Scientist

* Lawsuit Filed Against California Over High Stakes Test

Errant Protein Could Solve The Riddle Of Autism

http://www.abc.net.au/news/science/research/2001/05/item20010511035526_1.htm

A malfunctioning protein that regulates metal metabolism could be the

cause of autism, a debilitating developmental condition that afflicts

thousands of children, a study released Thursday said.

US researchers reported that a staggering 99 per cent of the

autistic children they studied showed a chemical imbalance in blood levels

of copper and zinc, suggesting that the protein family that regulates the

use of these two metals is malfunctioning.

The suspect metallothionein (MT) proteins control brain cell

development and are essential for ridding the body of certain toxins. Their

impairment could account for the stunted cognitive development and

gastrointestinal problems commonly seen in autistic children.

The study's author, Bill Walsh of the Pfeiffer Treatment Center, in

Naperville, Illinois, said the findings were so " extraordinarily abnormal "

that they immediately struck him.

Walsh presented his findings to the American Psychiatric

Association's annual conference in New Orleans.

If further research substantiated the theory, it could lead to a

quantum leap forward in our understanding of the disorder, he said.

" This might be central to the cause of autism, " explained Walsh. " I

think it will lead right to the autism gene and give us a roadmap for

therapy. "

To date, the medical community has not been able to arrive at a

consensus on the cause or best treatments for the condition, which typically

affects children under three, impairing their language and social skills and

often associated with a host of gastrointestinal problems.

Much of the debate has focused on the question of whether the

measles, mumps and rubella (MMR) vaccination may trigger the devastating

condition, which in some cases robs children of the linguistic and social

progress they have already made.

But recent studies, including one in March by the California

Department of Health Services which reviewed the data on all the autism

cases seen in the state over 14 years, appear to discredit that theory.

The question now is to determine whether the MT proteins are

genetically defective or disabled by a biochemical abnormality, which may

stem in part from environmental factors such as toxin poisoning, said Walsh.

In either case, doctors hope to stimulate the protein's production

and functioning by giving autistic children nutritional supplements.

But in any event, if the further studies planned by Walsh and his

colleagues confirm their theory, their work could lead to an early infant

screening-test for autism predisposition, and advanced treatments to correct

the metal-metabolism disorder.

The study of 503 autistic children was conducted at the Pfeiffer

Center, an institute which leads the field in research into biochemical

therapies for behavioural problems and mental conditions.

* * *

New Research Suggests Cause of Autism

[Another treatment of the same story as above. There is some different

information.]

http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104 & STORY=/www/story/05-10

-2001/0001490675 & EDATE=

PRNewswire - Autism -- a poorly understood genetic disorder present in

more than a half million Americans -- may be caused by a defect in metal

metabolism that impairs the development of the brain and can result in

hypersensitivity to toxic environmental substances. In a study of 503

autism patients, 99 percent exhibited evidence of this metabolic disorder,

according to information presented here today at the annual meeting of the

American Psychiatric Association.

Blood and urine analyses yielded evidence of a metallothionein (MT)

dysfunction in 499 of 503 patients (99 percent) diagnosed with autism

spectrum disorders, according to J. Walsh, Ph.D., biochemist and

chief scientist of the Pfeiffer Center, Naperville, Ill., and Anjum Usman,

M.D., a physician at the Center, who presented the findings in a

presentation at the APA meeting.

" MT is a family of proteins essential for many important processes in

the body, and a dysfunction in this system can explain most of the classic

symptoms observed in autism, " said Dr. Walsh. " An MT disorder may affect

the development of brain neurons and may cause impairments in the immune

system and gastrointestinal tract, along with hypersensitivity to toxic

metals, " he said.

The study included a search for distinctive chemical markers for the

major components of autism spectrum conditions, including classic autism,

Asperger's Disorder and pervasive development disorder with autistic

features. No substantive differences were found among these populations.

However all three populations exhibited a very high incidence of a severe

metal-metabolism disorder.

" A careful analysis indicated that all but 4 of the 503

autism-spectrum subjects exhibited evidence of a metal metabolism disorder

associated with MT functioning, " Dr. Walsh said. The study findings suggest

that the primary cause of autism may be an inborn error in MT functioning,

perhaps aggravated by an environmental insult, he said.

The study findings also suggest that autism may be caused by either a

genetic MT defect or a biochemical abnormality, which disables MT protein.

If correct, the study finding could lead to an early infant screening test

for autism predisposition, and advanced treatments to correct the

metal-metabolism disorders.

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* * *

Autism on the Rise

Multidisciplinary efforts aim at finding the biological basis for a complex

disease

[by DeFrancesco in The Scientist 15[10]:16, May 14, 2001.]

http://www.the-scientist.com/yr2001/may/research1_010514.html

The right image [not shown] shows positive functional activity in the

fusiform gyrus (FG) and superior temporal sulcus (STS) in a group of normal

subjects in response to faces, in comparison to the lack of functional

activity noted in these regions in autistic patients (left image). The T

value is a metric of the functional NMR signal intensity in relation to the

variance.

The rate of autism is rising. The number of reported cases has

increased 10-fold in the last few decades, from 1 in 2,500 in the 1970s to 1

in 250 in the 1990s. Researchers are looking everywhere for the reason--from

drinking water to the womb--with no clear-cut answer to date. In part, the

increased incidence can be attributed to a broader definition of autism,

which now includes milder forms of the disorder,1 as well as to better

diagnostics and greater public awareness.2 But scientists don't know if

these reasons explain the entire increase.

At a late-April conference entitled " Autism: Deciphering the Puzzle, "

developmental biologists, geneticists, and neurobiologists gathered to talk

about this complex disease. While scientists attending the conference at the

California Institute of Technology could not explain the huge jump in

incidence, they did voice some hope: there is progress in understanding the

condition's biological basis, along with the development of experimental

models, and it could lead to better treatments.

A Neurologist's Nightmare

Described by one participant as " a neurologist's nightmare, " autism

affects a cohort of complex behaviors, involving impaired language

development, the inability to interact socially, and repetitive and

restrictive behaviors.

Generally, autism is diagnosed in children aged 2 and older because

the behaviors can't be observed at an earlier age. But researchers are

working on improving the tools for diagnosing autism, particularly in young

children. As with many neurological diseases, including apraxia and fetal

alcohol syndrome, early intervention improves the prognosis.

Rodier, professor of obstetrics and gynecology at the

University of Rochester, described an early intervention test at the

conference that is used with infants. Devised by Bryson of York

University in Toronto, this test measures a child's ability to shift focus

from one stimulus to another. In the first part of the test, one light is

turned on, and then as a second light is turned on, the first is shut off.

All children will shift their focus from the first to the second light. In

the second part of the test, the first light is left on. Here, normal

children will disengage from the first to the second light, but autistic

children cannot make that shift.

Rodier showed dramatic video footage of a 5-year-old autistic child

attempting this task. A look of panic came across the child's face, as he

realized that he couldn't take his eyes off the first light. In contrast, a

severely retarded 6-month-old could refocus her gaze with no problem. One

research tool that has eluded workers in this field is an experimental

animal model for autism, because the diagnosis relies on human terms such as

eye contact, facial expressions, and speech. Bryson's test may be just the

ticket; it provides a glimpse into the nervous system but doesn't require

learning or intelligence.

In the Mind's Eye

Many parents of autistic children suffer a heart-breaking burden:

often, their youngsters are not emotionally connected to them. A recent

University of Washington study, presented to the Society for Research in

Child Development, showed that autistic children don't respond to faces,

which could explain the emotional distance from their parents. Measuring

brain activity with a net of external electrodes, Geraldine Dawson, director

of the University of Washington Autism Center, found that the brains of

autistic children were electrophysiologically silent when shown pictures of

their mothers, while they did respond to other pictures, such as their

favorite toys.

At the Caltech conference, Courchesne, professor of neurosciences

at the University of California, San Diego, presented live, deep-brain scans

that back Dawson's work. Using imaging techniques, Courchesne and co-workers

showed that the fusiform gyrus, the part of the brain involved with face

recognition, is not active when autistic children are shown pictures of

faces. Instead, in autistic children, each child displays a different

electrophysiological pattern. Why there is decreased activity in the

fusiform gyrus is unknown, but Pierce, the principal investigator,

offers several explanations. " One possibility is that limited exposure to

faces in patients with autism (perhaps due to innate preference, biases of

processing style, or learning) results in an underdevelopment or

maldevelopment of face-processing systems. Another reason is that the neural

substrates involved in face processing (e.g., fusiform gyrus or amygdala) is

abnormal in autism. " She made her comments after the conference.

Thalidomide Revisited

Most everyone is familiar with the haunting pictures from the 1960s of

so-called thalidomide babies, who were born with deformed limbs after their

mothers took this sedative while pregnant. Overlooked in the early studies

is that many thalidomide children are autistic--missed, no doubt, because

their parents and doctors were dealing with the more obvious and dramatic

limb deformities. But in 1994, Swedish researchers reported the surprising

finding that thalidomide children had a high incidence of autism,3 and for

developmental biologist Rodier, this was helpful news, because the Swedish

researchers identified when, during their pregnancies, the women took the

drug.

Armed with these results, Rodier is developing an animal model for the

kinds of brain abnormalities observed with autism, since she knows exactly

when in the developmental program she needs to intervene. And she has the

environmental agents to do it. Though thalidomide doesn't affect rodents in

the same way as humans, Rodier has found that valproic acid, a common

anti-seizure drug known to induce autism, causes brain damage in rodents,

and precisely in the places expected, based on what's known about this

disease.

Meeting organizer describes a promising experimental

system being developed in his lab at Caltech that is based on studies

linking prenatal infections and immune dysfunction with mental illness. In

developing a system that assesses how interactions between the immune system

and nervous system affect brain development, has observed

autistic-like behaviors in mice born to mothers exposed to influenza during

pregnancy using a battery of behavioral tests.

In one experiment, mice are dropped into a box. While normal mice move

around the box, frequently stretching to sniff the environment, mice born to

infected mothers stay in the corner, clinging to the wall and sniffing only

occasionally. Using this test and others, intends to pick apart

the immune response to see what proteins or factors might be involved in

explaining the offspring's odd behavior. The evidence for a genetic

component to autism is overwhelming and indisputable.4 Consider, for

example, that the parents of an autistic child are more likely to have a

second autistic child, as opposed to those who have unaffected children. In

a normal family, the likelihood is 0.4 percent; if there already is an

autistic child, the odds grow to 2 to 3 percent.

With identical twins, if one is autistic, the likelihood that the

second will have some form of autism is a staggering 90 percent; with

fraternal twins, the odds shrink to 2 to 3 percent. Strong sentiment exists,

particularly among the parents of autistic children, that environmental

factors also are involved here. One popular theory links immunizations,

particularly measles, mumps, rubella (MMR), with the onset of autism.

Researchers at the Caltech meeting summarily dismissed this notion, because

scientific evidence, they say, does not exist.

Several recent studies, including an Institute of Medicine report

issued April 23, did not show a correlation between MMR immunization and

autism.5 In a study published last February in the British Medical Journal,6

there was no abrupt increase in the incidence of autism after the MMR

vaccine was introduced. What about other environmental factors?

Hollander, professor of psychiatry at the Mt. Sinai School of Medicine and

Clinical Director of the Seaver Autism Research Center in New York City, is

looking at several factors. Noting that an unusually large number of women

at his clinic had pitocin-induced labor, Hollander is currently conducting a

survey of some 58,000 births recorded in a national perinatal database to

look for a connection between that drug and autism. Hollander also is

investigating the possibility that an infectious agent is involved.

He has found that in autistic children, a high expression level exists

of a particular B-cell marker, D8/17, which is associated with altered

sensitivity to streptococcus A. Though much research has been carried out,

there is still no complete answer, or answers, as to why more autistic

children exist today. " Cautious folks will say that it is really impossible

to say for sure what the reason is at this point, " says. " Given

the broadening of the diagnostic criteria, the heightened recognition of the

disorder by doctors, and the fact that parents only get state funds to help

with special education ... if the child has a diagnosis of a severe disorder

such as autism, we'll only be able to tell if this is a true rise in

incidence after the dust has settled. " DeFrancesco

(defrancesco1@...) is a contributing editor for The Scientist.

References 1. E. Fombonne, " The epidemiology of autism: a review, "

Psychological Medicine , 29: 769-86, 2000.

2. C. Lord et al., " Autism spectrum disorders, " Neuron 28(2): 355-63,

2001.

3. K. Strömland, K. et al., " Autism in thalidomide embryopathy: A

population study, " Developmental Medicine and Child Neurology, 36: 351-6,

1994.

4. A. , " Autism as a strongly genetic disorder: evidence from a

British twin study, " Psychological Medicine, 25:63-77, 1995.

5. " Immunization Safety Review: Measles-Mumps-Rubella Vaccine and

Autism, " Institute of Medicine, April 23, 2001.

6. J.A. Kaye et al., " Mumps, measles, and rubella vaccine and the

incidence of autism recorded by general practitioners; a time trend

analysis, " British Medical Journal, 322:460-3, 2001.

* * *

Lawsuit Filed Against California Over High Stakes Test

Lawsuit Alleges State Exit Exam Discriminates

[Thanks to Pete .]

http://www.wrightslaw.com/news/2001/CA_highstakes.htm OAKLAND, California.

May 8, 2001/Mercury News.

" In unprecedented action that could eventually affect hundreds of

thousands of disabled students statewide, Disability Rights Advocates filed

a lawsuit Tuesday against California's Department of Education, challenging

its high school exit exam, which they say discriminates against those with

learning disabilities. "

" The lawsuit, which seeks class-action status, charges that the exam

discriminates because it provides no alternate assessment, no procedure for

requesting accommodations and no process for appeals.

The suit claims the exam tests disabled students on material that they

have never been taught. As a result, the lawsuit says, the department has

“created chaos and confusion.” The lawsuit seeks corrective action to remedy

these alleged flaws in the system . . . "

" In addition to the state Department of Education and Superintendent

Delaine Eastin, the suit, specifically, names Fremont Unified School

District and its superintendent, Sharon . One of the three student

plaintiffs, 13-year-old Juleus Chapman, attends Fremont's Hopkins Junior

High School. "

" The suit was also filed on behalf of the Learning Disabilities

Association of California. "

For more information about this important case about " high stakes

testing, " go to: http://www.wrightslaw.com/news/2001/CA_highstakes.htm

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