Therapy likely to be far off, specialists say

By Ellen Barry, Globe Staff, 11/2/2002

ithin a year, researchers will probably identify the first ''strong candidate genes'' that make children vulnerable to autism, Joseph Daniel Buxbaum, who heads the neuropsychiatric lab at Mount Sinai Hospital in New York, said yesterday.

Buxbaum, who has spent five years searching for the genes, said that laboratories working on the genetic roots of autism have made surprising progress over the past year. Autism is a brain disorder that leaves children unable to communicate or form normal relationships.

''I go through periods of optimism and pessimism, and I've been optimistic for a good long time now,'' said Buxbaum, who spoke at a conference on the disorder sponsored by LADDERS, a neurological clinic affiliated with the Massachusetts General Hospital.

But he warned that families should not assume that the discovery of the first genes will translate into treatment or prevention over the short term or even within their children's lives.

''It's the first thread,'' said Buxbaum, an assistant professor of psychiatry at the Mount Sinai School of Medicine. ''Families want to know when the ball of yarn is going to unravel. Scientists want to know when it is going to start to unravel.''

The hunt for the autism gene, begun with great optimism in the mid-1990s, has proven far more difficult than expected, and many parents and advocates contend that it is caused by environmental factors such as vaccines or infections.

Diagnoses of autism - an inability to communicate and form relationships - are increasing nationwide, radically in some locations, although some scientists believe that better diagnosis may account for the sharp rise. A study commissioned by the California Legislature reported last month that autism had increased by 273 percent between 1987 and 1998.

Few brain disorders have been more perplexing than autism, which strikes at the age of 18 months to 3 years and leaves children isolated from the world around them.

Researchers studying twins have found that many, but not all, identical twins share the disorder, suggesting that genetic factors are important, but that environmental factors can make a child more vulnerable.

Meanwhile, lawsuits have proliferated as parents identified environmental causes for their children's illness, most commonly, a childhood measles vaccine that contains minute traces of a mercury preservative.

US Representative Dan Burton, Republican of Indiana, whose grandson has autism, urged a congressional inquiry into what he terms an epidemic.

Two years ago, researcher Buxbaum's hope to find the cause and a treatment for autism had reached a low ebb, even as advocacy for the disease grew stronger. Emerging from a successful quest for the genetic roots of Alzheimer's disease, he had expected to isolate three or four genes linked to autism in the course of a year or so. It didn't happen.

''It seemed like we weren't going to get it,'' he said. ''I was telling people to stay in the business just so that we would have a holding pattern.''

But the last year has brought increased collaboration between international research teams, increased funding, and better technology. By dividing sample sets according to special characteristics, researchers have found much stronger links between regions of the human genome and the illness. Once the first genes are identified, Buxbaum said, later genes should be identified with less time and effort.

Scientists from Tufts-New England Medical Center and Massachusetts General Hospital warned against attaching too much hope to the the research. Unlike sickle-cell disease or Tay-Sachs disease, autism has such complex causes that there is little likelihood of a simple prenatal screening test for the disease.

Even if researchers succeed in identifying genes that make children susceptible to autism, it is unclear whether the discovery would lead to the development of new therapies in the near future, Buxbaum said.

Susan Santangelo of the Psychiatric and Neurodevelopmental Unit at MGH said, ''If we find something that directly positive, we'll be extremely lucky.''

But if it turns out that the genes launch a process that begins very early in a child's development and affects an area deep inside the brain, then the prospect of developing a preventive therapy may seem more distant than ever, she said.

Santangelo said she is less optimistic that a major discovery will be coming in the next year. ''I kind of don't like to hear things like that, because it really is hard on the parents,'' she said.

Ellen Barry can be reached at barry@globe.com.

This story ran on page A4 of the Boston Globe on 11/2/2002.
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