Friday, May 25, 2012

Fetal Gene Abnormalities May Cause Autism

Source: http://www.ucsdguardian.org/component/k2/item/25751-fetal-gene-abnormalities-may-cause-autism

Wednesday May 23, 2012 - 10:35PM

Fetal Gene Abnormalities May Cause Autism

Written by Rebecca Horwitz

Researchers have discovered genetic pathways in autistic brains that affect its development and offer a possible explanation for how the disorder develops. Director of the Autism Center of Excellence at the UCSD School of Medicine Eric Courchesne led the study, published March 23 in PLoS Genetics. The study found that several of the genetic networks that play a role in the management of early brain development function abnormally in the frontal cortex of an autistic brain.


Courchesne and his team used frozen brain tissue from the prefrontal cortex of autistic children, aged two to four, and control children who are not autistic, who had passed away to analyze brain tissue gene expression. The prefrontal cortex is the part of the brain responsible for cognitive communication and social development, and its development is abnormal in autistic children. They found that a large number of genes that control the number of brain cells were expressed incorrectly.

Many studies have shown that brain cells in autistic individuals may be too small and undeveloped. After cells are born, they differentiate into specific types of brain cells that are in charge of the different types of information processing. The abnormalities in these cells occur in the second and third trimester of pregnancy, the time span during which most brain cells are created.

“This evidence indicates that biological abnormalities in autism began in the prenatal stage and that the biological abnormalities of autism are complex,” Courchesne said. “They involve a number of large networks or systems in genes and then the regulation of those systems with too much or too little gene activity in those genes is responsible.”

They found evidence that many of the abnormally expressed genes correctly copied DNA during cell divisions. This suggests that the DNA defects associated with autism may not be detected while cells are dividing during prenatal cell development.

“Those DNA defects may creep into new cells that are being generated during prenatal development,” Courchesne said. “Those DNA defects may alter the functional integrity of brain cells.”

The first set of genes that were functionally abnormal was the sets of genes that regulate the number of brain cells. Courchesne said this may explain why many people with autism have an excess number of brain cells in the prefrontal area, and why the abnormal activity involved in DNA checking and correction may explain why some brain cells do not function correctly.

The team then found abnormal activity of genes in the blocks of frontal tissue that regulate the organizational patterning of the brain. They found abnormal activity in the genes that regulate the further development of cells. Courchesne said they think this could explain why autism affects cognitive functions.

About a decade ago, it was discovered that at young ages, the majority of autistic individuals have a brain that is too big. As the child develops and matures, there appears to be a loss of brain tissue. Courchesne and his team found evidence that there may be a growing loss of neurons in autistic individuals. The normal spacing of neurons begins to become more irregular, suggesting irregular locations of loss due to loss of brain tissue.

The team then looked at adults with autism and found different signatures of gene activity that point to loss of cells and remodeling of brain conditions.

“What we don’t know is whether those changes are improving connections or removing maladaptation connections, we just don’t know,” Courchesne said. “But we do know there’s a different profile that suggests some kind of remodeling. And whether it’s ultimately beneficial or not remains for future studies to figure out.”

Another part of their study discovered evidence that would explain why autism is genetically different in every individual with autism. There was overlap within the network in the brain to other individuals with autism, but it was incomplete. Each person has his own set of genes within a network that were the most effective. Then another person has a somewhat overlapping, but different set of genes within the same network.

These genetic networks with abnormalities are the cause of autism. It can be confusing to understand the genes involved in autism because each person with autism has a different set of genes within the same network.

“That’s probably why it’s so hard to understand what’s been so hard to get at the genetic root basis of autism,” Courchesne said.
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Rebecca Horwitz

Rebecca Horwitz

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Wednesday, April 11, 2012

Nearing the end of the tunnel?

Source: http://www.boston.com/Boston/dailydose/2012/04/could-autism-reversed-with-pill/lk78SvP6Dn9qnR0lc3gvIM/index.html

Could autism be reversed with a pill?

04/11/2012 1:41 PM

By Karen Weintraub, Globe Correspondent

What if autism could be reversed with a pill?

A growing body of research in mice and a handful of people is finding that autism is not a degenerative disease like Alzheimer’s, but a changeable condition, like, say, epilepsy that can potentially be controlled.

A study out Wednesday in the journal Neuron found that medication could correct the health and behavior problems of mice with a genetic condition known to lead to autism in people. The drug, which acts on the synapses, or gaps, between brain cells, reversed a vast range of symptoms often associated with autism -- including lack of sociability, physical awkwardness, and hyperactivity.

Most surprising, the drug worked on adolescent mice, showing that these symptoms are reversible even after the critical period of early brain development.

“I was thrilled,” said Mark Bear, the MIT neuroscientist who led the research.

Bear helped found a company, Seaside Therapeutics, which is currently studying a similar drug in people with Fragile X, a genetic condition that often leads to autism. The mice had the same genetic change as the people in the study. Roche and Novartis are also studying similar medications, with effectiveness trials due to be completed in about a year.

“I can’t tell you how exciting it is right now, and how anxiously I am awaiting the impact of these clinical trials,” Bear said. “It seems that in Fragile X and maybe other causes of autism there is essentially a metabolic problem.”

The problem in Fragile X, Bear said, seems to be that there are too many proteins being produced in the junctures between brain cells. Flooded with proteins from one brain cell, the receptors at another don’t know which protein to accept, and, essentially, a traffic jam results.

Bear said he was amazed, several years ago, when he realized that a tie-up between brain cells could cause the full range of symptoms found in autism.

“It truly is extraordinary that this receptor seems to give rise to so many aspects of the disease,” he said.

Bear’s isn’t the only research to suggest that autism may be reversible, even beyond childhood.

In a 2007 study in the journal Science (covered in The Globe at the time), Adrian Bird from Edinburgh University reversed symptoms in adult mice with a different genetic glitch -- which leads to another autism-like condition in people, called Rett Syndrome. Using medication to turn back on the gene that is turned off in Rett Syndrome “leads to striking loss of advanced neurological symptoms in both immature and mature adult animals,” Bird’s study concluded.

Last month, another study -- this time in Nature -- found that Rett’s devastating symptoms could be stopped in mice if they got a bone marrow transplant. This suggests that the immune system plays a role in Rett.

Mice with Rett syndrome normally live about weeks, but given a bone marrow transplant from healthy mice, they live much longer -- at least some of them are still alive nearly a year later, said Noel C. Derecki, the research fellow who led the study at the School of Medicine at the University of Virginia.

Derecki, and senior author Jonathan Kipnis, an associate professor at Virginia, said their work suggests that the loss of the MECP2 gene seen in Rett impairs the brain’s ability to “take out the trash.”

“These cells need to be cleaned up, so debris doesn’t build up,” said Derecki, whose grandfather ran a garbage collection business. By reinforcing the immune system with a bone marrow transplant, the researchers restored the mouse brain’s ability to take out the trash.

Again, their conclusion was that autism is likely changeable throughout life -- that the behavior we see in people with autism is due to brain malfunctions but not brain damage.

The next step is to take their research into people, figuring out what kind of treatment will be most helpful. It’s not yet clear either whether the findings in Rett and Fragile X will extend to the roughly 85 percent of those with autism who don’t have an obvious genetic glitch.

Bear says that the findings of reversibility in older animals is good news for drug testing, because it’s much easier to study drugs on adults than children.

Also, he said, a drug alone may not be enough.

Mice given the drug for four months improved far more than those given it for just a month -- suggesting, he said, that the brain needs to adapt once its biological problems have been resolved.

In people, Bear said, “it’s not just the drug that’s going to lift the veil [of autism], but it’s going to allow the veil to be lifted with appropriate behavioral therapy. And that’s really what we’re aiming for.”

Karen Weintraub can be reached at Karen@KarenWeintraub.com.
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Sunday, April 1, 2012

Chromosome 16

Source: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2012/03/30/MNPU1NS5LL.DTL&type=science

Autism: UCSF zeroes in on rare chromosome defect

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Michael Macor / The Chronicle

Christopher Mahar, a 14-year-old from Oregon whose autism may be caused by a rare chromosome defect, prepares for a scan at UCSF to follow his brain activity.

When her son was diagnosed with a rare chromosome defect three years ago, it was something of a relief for Theresa Mahar.

Finally, she had an explanation. Christopher, now 14, had obvious developmental delays and intellectual disabilities. He had behavior problems and struggled in school. He'd been assigned so many diagnoses over the years - almost all of them related to autism - that it was sometimes hard to keep up.

Then a genetic test revealed the defect to chromosome 16 - one of the 23 chromosomes that make up every person's DNA - and it explained, perhaps, the cause of Christopher's autism.

"It's something to hold on to," Theresa Mahar said. "It's something to blame."

Mahar and her family came to San Francisco from Hillsboro, Ore., this week to participate in an unusual study at UCSF - to map in great detail the brains of people who have a defect to chromosome 16.

The study is one of the first in which autism researchers are narrowing their focus into one of the few known causes of the disorder. That's important, scientists say, because autism is such a difficult condition to define - the symptoms can vary widely from patient to patient, and the causes are often impossible to determine.

Different mechanisms

Autism may be a collection of similar conditions, rather than one single disorder, researchers say. That means that studying patients with autism as it's now defined often produces mixed results - the brain scan of a child with one genetic cause of autism may look very different from the scan of an autistic child with no genetic cause.

"It may be that there are different mechanisms depending on the underlying biology of autism," said Dr. Elliott Sherr, who heads the study at UCSF. "If you study a group and they have the same biology and underlying genetics, in theory that should clean things up a bit."

The study at UCSF is part of a five-center clinical trial funded by the private Simons Foundation. Researchers plan to study at least 200 volunteers with the chromosome 16 defect.

Both Christopher and his father, Robert Mahar, have the same defect. In their case, a tiny section of the chromosome known as the 16p11.2 segment is duplicated. Robert Mahar is not diagnosed with autism, but he struggled in school and now wonders if he had learning disabilities related to chromosome 16.

Scientists were able to identify the connection between the specific chromosome 16 defects and autism using relatively new supersensitive genetic testing tools. Chromosome 16 defects are thought to cause about 1 percent of all cases of autism in the United States, affecting roughly 30,000 children.

On Wednesday and Thursday this week, both Christopher and Robert Mahar had a magnetic resonance imaging (MRI) scan to map the structure of their brains. They also had a magnetoencephalograph (MEG) scan, which follows brain activity and lets scientists see what parts of the brain "light up" when patients are doing certain tasks or thinking about specific topics.

Seeking treatment clues

For example, one problem often associated with autism is an inability to tell faces apart. So Christopher and his father spent several minutes in the MEG scanner looking at pictures of faces while doctors studied their brain activity. The results will be compared with scans of people without the chromosome defect.

Sherr said he hopes the collection of scans from similar patients will paint a clear picture of what happens in the brains of people with this specific defect. Then, scientists can use that information to get a better understanding of what might be causing autism in those patients - and better yet, how it might be treated.

For now, few standard treatments exist for autism beyond behavioral therapy. Some drugs work, but not for everyone, and often not very well. Even the behavioral therapy could be better tailored to the individual patient if doctors better understood what was causing the problem, said Dr. Linda Lotspeich, a psychiatrist with the Autism and Developmental Disorders Clinic at Lucile Packard Children's Hospital at Stanford.

"Those targeted treatments could be more sophisticated behavioral treatments than we currently have, and they could be biological treatments," Lotspeich said.

The Mahars said they don't expect the current research to help their son immediately. It's been frustrating trying to get help for Christopher, Theresa Mahar said. Even finding a doctor who has heard of the chromosome 16 defect has been tough.

Sitting in a conference room at the end of the day Wednesday, the Mahars were exhausted. Christopher and Robert Mahar had been going through tests all morning and afternoon, and Theresa Mahar and the couple's daughter, Caitlin, were stuck at the hospital.

Helping other children

When his last psychiatric evaluation was done, Christopher begged for a toy from the scientists and asked if the family could go to the zoo. Maybe on another trip, Theresa Mahar said - they still had another day of testing before going home.

She said she understands that Christopher may never directly benefit from the research being done now, and Robert Mahar said the goal is to "figure out something for other kids down the road."

"But for my part, participating in this research is being selfish," Theresa Mahar said. "It's about how we can help my son."

Details on disorder

For more information about the chromosome 16 and autism research at UCSF, including how to volunteer for the study, go to links.sfgate.com/ZLIP.

Erin Allday is a San Francisco Chronicle staff writer. eallday@sfchronicle.com

This article appeared on page A - 1 of the San Francisco Chronicle


Read more: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2012/03/29/BAPU1NS5LL.DTL#ixzz1qpeeUA4U
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Saturday, March 31, 2012

My thoughts about my child with autism

Some of my thoughts that I posted:

We are family who has one child with autism. It is not a smooth life but we learned how to cope with the challenges. Sometimes, there are always the downside due to behavior issues. However, we did not limit our son on what the school can teach. The schools in the US consider students with autism as dumb. They may not say it bluntly but since they can not immediately give answers nor be able to process information as fast as the neuro-typical children, they are always left behind in the curriculum. The parents have to fight this hard battle in order for the child with autism to be educated. We did not leave our son in the hands of the school to learn. If we did, he might be one of those who can not even go beyond Kindergarten level. We never believe in medicating our child just to conform with the etiquette of the society.

The author's purpose is not exactly to lighten up the load of the families who have kids with autism. It tells you that some of these kids with autism can really manage something that neuro-typicals can not. Every child with autism is as normal as the next door typical kid BUT since the society have managed to segregate them without regards to what they can really do, many of the children now with autism will really grow up as adults with autism who will be a burden to society since that is how they have been brought up.

Mr. _______, am glad your daughter is not on the lower end of the spectrum. That is good news. You just need to be patient with her and never lose the hope. Mind you, my spouse hardly knows how to tie shoelaces and buying slip-on shoes solved the problem. Just have to see the flip side. My spouse is not on the spectrum and in fact, a director in a very big bank. There are those little and many things still that hound our son but we have our feet on the ground and really strive for him to comprehend better. Every small things he can do, is an achievement for us (even though we want him to be faster). :))

Mr. _______, oh, where can we find a person like you in the school system? You see, we have been to 3 states and they basically treat children with autism all the same. Just imagine, teaching over and over Kindergarten stuffs when he is in higher grades just because he does not communicate? He talks but hardly communicates. He is too independent without a voice. We have seen classrooms of students with autism especially the ones on the ABA classes that are so barren that the empty space is suffocating us. We try to remind them of the phrase, "the mind is a terrible thing to waste." They respond with we see things in real terms only. In one classroom, the students with autism are just playing in the middle of school hours? There was not a single book in the classroom nor are there any writings on the board. In another classroom, they showed us their students with autism who are using the computers and are navigating in websites. However, they locked them with starfall website (K and 1 stuffs) and they are in 5th grade? We have met so many teachers and they are all fearing that students with autism who are taking the nationwide tests because they will surely flunk? Hence, we are on our toes with the school districts that we have encountered. By the way, his K teacher told me, he can not add one apple and one apple (two drawings of apple) so he can not do addition much more subtraction (We were asking the teacher to give him materials to compute in addition and subtraction). If we have believed the teacher, then our son will be forever dumb (We have to be blunt here because in all the schools we have been, their perception is that students with autism can not go higher in life. Hence, they want to lock them with life skills teaching.) with adding one apple and one apple. By 2nd grade, he is very good in multiplication more than the students of his age and older.
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