Wednesday, July 27, 2005

Autism Spectrum Disorder gene study

A SINGLE gene that appears to increase the risk of a person developing autism when mutated has been identified by scientists, suggesting new approaches to diagnosing and treating the condition.
Research in the United States has revealed that many cases of autism may be triggered in similar fashion to diseases such as cystic fibrosis — in which one gene goes wrong, but in a multitude of different ways. The work at Vanderbilt University in Tennessee suggests that it may be possible to develop a blood test that can pinpoint the probable cause, which could have important implications for treatment.

It is known that some children and adults with autism respond positively to a class of antidepressant drugs called selective serotonin reuptake inhibitors (SSRIs), which includes Prozac and Seroxat.
James Sutcliffe, a research leader, said: “You might be able to predict which kids would respond positively to particular SSRI medications.” The gene that has been implicated in autism is the serotonin transporter gene, known as SERT. This plays a key role in regulating the brain’s levels of serotonin, a signalling chemical involved in mood, impulsive behaviour and sleep.
Scientists have known for some time that about 25 per cent of people with autism have elevated levels of serotonin in their blood, suggesting a possible link to the disorder.
Two new studies by the Vanderbilt team have shed light on how the SERT gene might influence autism. The first, published in the American Journal of Human Genetics, shows that several mutations in SERT may be risk factors in autism. The second, published in Proceedings of the National Academy of Sciences, suggests a possible mechanism by which these mutations may have adverse effects.
Randy Blakely, who led the studies with Dr Sutcliffe, said: “Autism has such a high genetic risk, but these new findings suggest that there may be many variants of individual genes at work. We now have concrete evidence that the SERT gene is a risk factor in autism. Perhaps more importantly, we also have new pathways that could have some therapeutic end points.”
The protein produced by the SERT gene normally has the job of mopping up excess serotonin in the brain. The Vanderbilt team, however, has shown that several of the proteins produced by mutant versions of the gene cannot be properly “read” by cells, and this may play a part in autism.
“We were stunned because the cell just can’t talk to these SERT proteins in a normal way,” Dr Blakely said. “Although it’s impossible to extrapolate from a molecule to a person, it is striking that these mutations, which do not allow proper communication with SERT, show up in a disorder fraught with communication problems.”
Another promising finding is that certain key signalling pathways go wrong with mutated SERT genes. As drugs that target these pathways are being investigated to treat cancer and inflammation, these might have potential for autism. “This is a potential therapeutic area we hadn’t envisioned before,” Dr Blakely said.