Scientists eye an enzyme as target in fighting autism

CHICAGO (AFP) - US researchers have reversed the symptoms of mental retardation and autism in mice by inhibiting an enzyme that affects the connections between brain cells, researchers said Wednesday.

In a series of experiments on mice, the MIT investigators showed that they could undo the brain damage seen in a condition called Fragile X syndrome by inhibiting a key brain chemical called PAK.

In humans, Fragile X syndrome (FXS) is the leading cause of mental retardation and the most common genetic cause of autism -- the complex and devastating developmental disorder that is now being diagnosed in increasing numbers of children.

The study raises the intriguing possibility that the brain damage seen in children with the condition can be rolled back and identifies a specific target for potential drug therapies.

"It opens up a new avenue for drug research to treat this condition," said Susumu Tonegawa, a neuroscientist at the Massachusetts Institute of Technology in Cambridge, Massachusetts, and lead author of the paper.

MIT researchers began by creating a batch of mice that had been genetically modified to have Fragile X, a condition in which the neurons of the brain are structurally abnormal and functionally impaired compared to regular nerve cells.

These transgenic mice had many of the behavioral problems seen in kids with the condition: hyperactivity, attention deficits, repetitive behaviors and poor social skills.

The investigators then cross-bred these mice with another batch of mice that had been genetically modified to inhibit the activity of the PAK (p21-activated kinase) enzyme which is instrumental in shaping the formation of neuronal connections in the brain.

The researchers knew that when PAK was inactivated, the mice developed neurons that had short, fat dendritic spines, with a higher-than-usual capacity for relaying the electrical impulses that pass between brain cells.

In other words, the shape and function of the dendritic spines in the PAK mice was just the reverse of those seen in the brain cells of the mice with Fragile X syndrome.

The researchers gambled that the two abnormalities would cancel each other out, and that's exactly what the experiment showed.

The cross-bred mice had been genetically engineered so that the inactivation of the PAK enzyme began two weeks into the mouse's life cycle, which in human terms would be several years after birth.

Tests and autopsies showed that the PAK-blocking action restored electrical communication between neurons in the brains of the double mutant mice, correcting their behavioral abnormalities in the process.

"This is very exciting because it suggests that PAK inhibitors could be used for therapeutic purposes to reverse already established mental impairments in fragile X children," said Eric Klann, a professor at New York University's Center for Neural Science.

The study was conducted by Tonegawa and a postdoctoral student at MIT's Picower Institute for Learning and Memory and appears in this week's edition of the Proceedings of the National Academy of Sciences.

Court to focus on vaccine, autism Monday

WASHINGTON - Thousands of families that allege vaccines caused their children's autism are preparing for their day in court, which could bring them vindication and compensation.

Since 1999, more than 4,800 families have filed claims with the government alleging their children contracted autism as a result of routine vaccinations. Most contend that a preservative called thimerosal is to blame for the impaired social interaction typical of the disorder.

Previously, large scientific studies have found no association between autism and vaccines containing thimerosal.

But many parents say their children's symptoms did not show up until after their children received the vaccines, required by many states for admission to school. If they prevail in the courts, the families are entitled to compensation from a multibillion-dollar trust fund.

The first of what eventually could be nine test cases from those claims is the subject of the hearing opening Monday in the U.S. Court of Federal Claims. Three special masters appointed by the court will preside over the hearing, expected to last through June 29.

Autism is characterized by impaired social interaction. Those affected often have trouble communicating, and they exhibit unusual or severely limited activities and interests. Classic symptoms of mercury poisoning include anxiety, fatigue and abnormal irritation, as well as cognitive and motor dysfunction.

Monday's case addresses the theory that the cause of autism is the measles, mumps and rubella vaccine in combination with other vaccines containing thimerosal. The preservative, about 50 percent mercury by weight, is no longer found in routine childhood vaccines but is used in some flu shots.

In July 1999, the U.S. government asked vaccine manufacturers to eliminate or reduce, as expeditiously as possible, the mercury content of their vaccines to avoid any possibility of infants who receive vaccines being exposed to more mercury than is recommended by federal guidelines.

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On the Net:

U.S. Court of Federal Claims: http://www.uscfc.uscourts.gov

Mild autism has 'selective advantages'

Asperger Syndrome can improve concentration

By Sue Herera

Anchor

CNBC

Updated: 5:42 p.m. CT Feb 25, 2005

What happens when children with autism grow up? It may sound paradoxical, but some with the mildest form, Asperger Syndrome, may turn out to be stars.

People with Asperger's often have extreme difficulty interacting socially, preferring to focus on narrow fields of interest. But often they're able to pursue those interests with great intensity. Geniuses throughout history, including Albert Einstein, Andy Warhol and Emily Dickinson, have all been thought to have had Asperger's. And now Nobel Laureate Vernon Smith has decided to speak openly about what he calls the deficiencies and the selective advantages of Asperger's.

“I can switch out and go into a concentrated mode and the world is completely shut out,” he said in a recent interview. “If I'm writing something, nothing else exists.”

Smith received the Nobel Prize in 2002 for inventing the field of experimental economics, which uses laboratory methods to test economic theories. Smith says his capacity for deep concentration contributed to his ability to win the Nobel Prize.

“Perhaps even more importantly, I don't have any trouble thinking outside the box,” he said. “I don't feel any social pressure to do things the way other people are doing them, professionally. And so I have been more open to different ways of looking at a lot of the problems in economics."

CNBC: Did you feel like you seemed strange in the eyes of other people?
Smith: Oh, yes.
CNBC: How so?
Smith: Sometimes I'm described as "not there" in a social situation. You know, a social situation that lasts for a couple of hours I find it to be a tremendous amount of strain, so I've been known just to go to bed and read.
CNBC: What led you to teaching? Teaching is very social and you said earlier you don't do well in social situations.
Smith: Teaching ... has forced me into being more social, but it's on professional dimensions that I'm comfortable with. We're talking about things that I have a lot of experience with, and I can relate to students very easily in that mode.
CNBC: Because they're in your world?
Smith: Yes, exactly, that's a good way to put it, they're in my world. And there are maybe worlds out there that I don't understand, so I don't go there.

Smiths' wife, Candace, says it hard at times to understand why her husband can't be part of her emotional world.

"He might not always know what he feels," she said. "In fact, many times he doesn't. He'll say, 'I don't know. What do you mean? ..."

Smith says she's found comfort in the Asperger's label because it's helped put some of her husband's actions into perspective.

"If you didn't have these words like autism or Asperger's as entry words into your own experience and understanding then you could categorize a child or adult as unemotional, cold, insensitive," she said. "Many people don't understand Vernon and they conclude wrongly about him."

Some doctors who treat people with Asperger's, like Dr. Ami Klin at Yale University, say Smith's success is not typical of people with this disability.

"The vast majority of individuals with Asperger Syndrome need help — without that help they won't be able to do very well," he said. "The individuals that I know have to overcome a great deal of difficulty to maximize their potential and get the things in life they deserve."

CNBC: There are people who think that a number of highly influential executives may have Asperger's or are on the autism spectrum. Is that society making a judgement or is it coming to realize that there are different kinds of minds?
Smith: I think it's different kinds of minds, and the recognition that certain mental deficiencies may actually have some selective advantages in terms of activities. We've lost a lot of the barriers that have to do with skin color and with various other characteristics. But there's still not sufficient recognition of mental diversities. And we don't all have to think alike to be communal and to live in a productive and satisfying world.

Bob Wright: ‘I want my grandson back’

The vice chairman of GE and chairman and CEO of NBC Universal talks about his family's personal crusade to cure autism

By Bob Wright

Vice chairman of GE and chairman and CEO of NBC Universal

TODAY

Updated: 9:34 a.m. CT Feb 25, 2005

Autism is in the news, and it’s about time. On Monday, the Centers for Disease Control launched a new education initiative designed to educate parents of young children about the early signs of developmental disorders such as autism. Among mainstream print media, The New York Times is following this story closely, publishing more than two dozen articles on autism in the past six months. Newsweek has made autism the cover story of its latest issue. NBC News has devoted significant airtime this week to exploring every aspect of this disorder, with reports on “Today,” “Nightly News,” CNBC, MSNBC, Telemundo, the owned NBC stations, as well as on this news Web site. Autism has also been featured recently in entertainment shows such as “Without a Trace” and “Scrubs.”

Why the flurry of interest? Here’s a clue: 1 in 166. That’s the chance a baby born today will have autism. This represents a dramatic increase from a decade ago, when experts estimated the incidence rate to be 1 in 2,500.

What explains this sudden increase? No one knows for sure. What is clear, however, is that autism demands more public awareness, more understanding, and more funding, both private and public.

I know the people of NBC News take great pride in the work they have done this week in shedding light on the mystery of autism. I’m grateful for their efforts. I say this not only as the head of NBC Universal but also as someone who has a personal stake in this issue.

Last March, our grandson was diagnosed with autism. We have watched helplessly as an apparently normal toddler lost his ability to interact with the outside world. My wife, Suzanne, likens it to a kidnapping, as if someone has taken away the life he was meant to live. We all want nothing more than to have him back where he belongs, restored to his family.

Since the diagnosis, our family has been on a mission to learn all we could about autism, and help ensure our grandchild receives the best therapy and treatments available. Frankly, it’s been a difficult and frustrating challenge. We discovered, to our surprise, just how scarce the resources are for parents dealing with autism, and how thin the knowledge. We had so many questions, and instead of answers, we found a bewildering array of theories and guesses. We found it hard to believe that a disorder with the frequency of autism commands so little public attention and such meager resources devoted to research, compared to other, less common childhood disorders.

Autism is the most widely diagnosed developmental disability in the nation, yet autism research receives only $15 million per year from private sources, compared to more than $500 million for conditions like childhood cancers, muscular dystrophy, juvenile diabetes, and cystic fibrosis — all of which combined together are less common than autism.

To help close this gap in awareness and resources, we are announcing the launch of a new organization, Autism Speaks, devoted to educating the public about autism, facilitating and funding research, motivating private and governmental resources, and, ultimately, helping to find a cure for autism.

Autism Speaks is dedicated to helping families find answers. But neurological disorders are complex, and autism won’t yield its secrets without a struggle. One significant way Autism Speaks will help will be by spearheading the assembly of a large central database of children with autism that will provide, for the first time, the standardized medical records that researchers need to conduct accurate clinical trials. We believe this will facilitate the large-scale longitudinal studies and clinical trials that will help lead us to a cure.

Yes, I’m keeping my day job. But I also want my grandson back. So, for as long as it takes, Suzanne and I are going to be devoting whatever extra energy we can muster to helping Autism Speaks achieve its goals. Autism is a vexing puzzle. We are committed to finding the answers.

Bob Wright is the vice chairman of GE and chairman and CEO of NBC Universal, the parent company of NBC News. For more information about Autism Speaks, visit www.autismspeaks.org or call 1-888-AUTISM-5.

I'm not so interested in a 'cure' as I am in prevention. If I was offered the chance today to 'cure' my son, I don't know if I would do it. My son is a unique individual who is very special, I wouldn't want to take anything away from him. - Marc

Fact file - Autism signs and symptoms

Children with autism and other autism spectrum disorders typically display a range of identifiable symptoms. By being aware of these signs, parents can help spot the disorder at an earlier age, which greatly improves a child’s overall prognosis.

Communication

-- Delay in, or total lack of, development of spoken language
-- Difficulty initiating conversation
-- Echolalia (repeating words or phrases instead of using normal language)
-- Doesn’t respond to name
-- Doesn’t use or respond to gestures and other nonverbal cues

Social interaction

-- Doesn’t point to objects or show them to others
-- Doesn’t make eye contact at appropriate times
-- Doesn’t look at other people’s faces as much
-- Doesn’t respond to facial expressions or body language
-- Doesn’t smile back at others
-- Lack of peer relationships appropriate to age level
-- Less interest in other children
-- Not motivated by praise or physical affection
-- Doesn’t clearly demonstrate sympathy or empathy

Behaviors

-- Engages in highly repetitive play
-- Obsessively preoccupied with a specific interest or object
-- Lack of make-believe or imitative play
-- Dependent on routines, rituals and familiarity
-- Repetitive body movements (hand or finger flapping, eye rolling, twisting, spinning, rocking, etc.)
-- Preoccupation with parts of objects
-- Easily overstimulated by noises, crowds or lights
-- Extreme dislike of certain sounds, textures or situations
-- Doesn’t have strong response to pain

Parents blaming autism on vaccines go to court

Scientists dispute claims that mercury in shots led to kids’ condition

WASHINGTON - Science has spoken when it comes to the theory that some childhood vaccines can cause autism. They don’t, the Institute of Medicine concluded three years ago.

Soon, it will be the court’s turn to speak.

More than 4,800 claims have been filed against the federal government during the past six years alleging that a child contracted autism as a result of a vaccine. The first test case from among those claims will be the subject of a hearing that was to begin next Monday in a little-known “People’s Court” — the U.S. Court of Federal Claims. A special master appointed by the court will hear the case.

For the parents filing a claim, there is the potential for vindication, and for financial redress.

The test case addresses the theory that the cause of autism is the measles, mumps and rubella vaccine in combination with other vaccines containing the preservative thimerosal. That preservative, which contains a form of mercury, is no longer in routine childhood vaccines. However, it is used in influenza vaccines.

One of the parents who has filed a claim against the federal government and has great interest in the case is Scott Bono of Durham, N.C. His son, Jackson, 18, has autism. While acknowledging the findings of the IOM’s study, Bono believes those findings were preordained by the federal government.

“The charge before the IOM committee was: ‘You’re not going to find anything wrong here,”’ Bono said.

He said that parents of children with autism have been marginalized, but they see specific outcomes in their children that are consistent with exposure to mercury. And those outcomes did not present themselves until after they received their vaccinations. In short, the children tell the story better than the numbers, he said.

“It’s a thrill in the sense that, for the first time, the stories of these children are going to be heard in court,” Bono said.

No correlations found
In July 1999, the U.S. government asked vaccine manufacturers to eliminate or reduce, as expeditiously as possible, the mercury content of their vaccines to avoid any possibility of infants who receive vaccines being exposed to more mercury than is recommended by federal guidelines.

Dr. Paul Offit, who developed a vaccine for the rotovirus, is chief of the division of infectious diseases at the Children’s Hospital of Philadelphia. He said epidemiological studies pick up minute, almost invisible differences in the populations that have received a vaccine versus those that have not.

For example, a swine flu vaccine in the 1970s caused the sometimes paralyzing Guillain-Barre syndrome in 1 out of 100,000 cases, he said.

But no such correlations have been found for autism, which affects about 1 out of 150 children, he said.

“It should be easily picked up,” he said. “It hasn’t been and the reason it hasn’t been is because vaccines do not cause autism.”

Offit said mercury is part of the natural environment. There’s no escaping it and, in fact, children will get more mercury from breast milk than they get from a vaccine. Yet, he’s frustrated when he hears lawmakers speak of having zero tolerance for mercury.

“On this planet you can’t have zero tolerance for mercury,” he said. “You would have to move to another planet.”

Working too closely?
Autism is characterized by impaired social interaction. Those affected often have trouble communicating, and they exhibit unusual or severely limited activities and interests. Meanwhile, classic symptoms of mercury poisoning include anxiety, fatigue and abnormal irritation, as well as cognitive and motor dysfunction.

The report from the Institute of Medicine pointed to five large studies, here and abroad, that tracked thousands of children since 2001 and found no association between autism and vaccines containing the preservative thimerosal.

Members of the National Autism Association see drug manufacturers and the federal government as working too closely together to the point that the federal government is working to protect the industry from liability. The association says its mission is to raise awareness of environmental toxins as causing neurological damage that often results in an autism or related diagnosis.

Bono, a member of the association, said he doesn’t believe his son was intentionally poisoned.

“I just want someone to step up and say, ‘You’re right, this did happen,”’ he said.

During the hearing, lawyers for the parents were expected to present their expert testimony during the first week. Then lawyers representing the federal government were expected to present their case. The hearing was to be open to the public.

Officials planned to post transcripts on the court’s Web site about 24 hours after each day’s proceedings.