When Michael Giangregorio's sons grow up, their father wants to be able to tell them that the autism now affecting the younger of the two, 5-year-old Nicholas, won't be handed down to their children.
Doctors have long known autism runs in families. Now, scientists have scanned DNA from 1,168 families with multiple cases, the largest such group ever assembled, and identified gene variants that could one day spur treatments for a disorder that leaves about 1 in 150 US children uncommunicative, cut off emotionally from the world around them.
The findings, announced today, include a deleted gene, called neurexin 1, that enables communication between neurons, the nerve cells in the brain that transmit information to the body through chemical and electrical signals. The researchers also found variants in two chromosomes that have never before been linked with the spectrum of similar disorders that includes autism and Asperger's Syndrome. „This is the most ambitious effort yet to find the locations of genes that may confer vulnerability to autism, revealing clues that will likely influence the direction of autism research for years to come,” said Elias Zerhouni, director of the US National Institutes of Health in Bethesda, Maryland, in a statement yesterday.
The NIH helped sponsor the work done by 120 scientists and 50 institutions in l9 countries who began work in 2002, a group known as the Autism Genome Project Consortium. Their findings will be published in the journal Nature Genetics. The hope is that by mapping genetic flaws tied to the disorders, scientists will be able to better understand how they work and determine whether they can be fixed, said Bernie Devlin, associate professor of psychiatry and human genetics at the University of Pittsburgh, and an author of the study.
„We'd like to think that eventually we'll be able to pinpoint individual genes that affect certain symptoms and treat them, sure” Devlin said in a telephone interview yesterday. „That's a ways away, of course, but it's something we're working toward.” Devlin said a report earlier this month showing that manipulation of genes in mice ended symptoms of Rett Syndrome, a rare genetic disease related to autism, suggests they may be on the right track, even though the spectrum of autism disorders seen in humans offers a much tougher target. „The finding we're announcing is just a first step,” he said.
„We have funding to continue working, and I'd be surprised if we don't have another big announcement within a year. While we're looking at 10,000 SNPs now, we will be looking at 500,000 or a million going forward.” SNPs, or single nucleotide polymorphisms, are the variations in DNA that make each individual unique.
The new findings combined two scientific methods, said Andy Shih, the chief science officer for Autism Speaks, a New York-based nonprofit advocacy group that also helped fund the study. This included traditional inheritance studies and new technology that searches for changes in the „architecture of chromosomes,” the long strings of genetic and other material that make up the human genome, Shih said in a telephone interview yesterday.
The study pinpointed previously unknown links to the disorders on chromosomes 11 and 15, and long-suspected connections in other chromosomes known to carry so-called neurotransmitter genes. That included deletion of the neurexin 1 gene that's involved in communication between so-called glutamate neurons in the brain. „That part wasn't a surprise,” Shih said.
„It makes sense that genes might be implicated that effect cell-to-cell communication, given what we know about autism.” The fact that a spectrum of similar disorders exists speaks to how complicated the genetic aspects may be, Shih said.
„Deficits can be quite varied from child to child, which means that genes in certain pathways might be affected in different ways,” he said. In some cases, the deficits can lead to severe developmental disability. While other children can communicate at a higher level, they often don't socialize easily with others and exhibit learning disabilities. „There might be different genetic combinations among families that affect the disorder in terms of the severity or nature of the deficits,” Shih said. „That means it could be a while before we sort out anything resembling a treatment.”
There are also environmental factors involved, he said, adding, „It's really quite a puzzle.” For Michael Giangregorio, it is a puzzle his family lives with every day. Giangregorio, who resides in Merrick, New York, said his son Nicholas was diagnosed with autism at about 16 months. His son Michael, who is 7, doesn't have autism, he said. When Nicholas was first diagnosed, health officials said that about 1 in 250 children had autism.
This month, the US Centers for Disease Control and Prevention in Atlanta released new figures acknowledging the prevalence has increased to 1 in 150. Giangregorio said there also a growing awareness about autism in the community at large.
„It used to be you didn't know where to go, what to do, who to talk with,” Giangregorio said in a telephone interview yesterday. „Awareness has grown 100-fold. There's a national understanding that this is something we need to solve.” That increased awareness is leading to a raft of new studies on the disorders, now largely treated with behavioral rather than biological therapies. While Michael has made progress with behavioral therapies, there is much work to be done in the future, Giangregorio said.
„Right now, the success of the biological treatments are largely anecdotal; we're not sure what's happened there yet,” said Shih. „There has been success with behavioral treatments, particularly when intervention is early.” Giangregorio said he's looking forward to a day „when my oldest comes to me and tells me he wants to get married. I'm hopeful that the work being done right now will enable me to tell him that everything is going to be all right. We've figured this thing out.” (Bloomberg)