Irreversible only for now?
Most people know Down syndrome is a genetic disorder that causes irreversible mental retardation. But that description may not be true in the future.
Scientists have pounced on the revolutionary idea that Down syndrome -- the most common genetic cause of mental retardation -- can be treated. First, they must understand the biological cause of the condition, down to the specific genes responsible for the varied symptoms. Then, they hope, they’ll be able to reverse or eliminate related problems with cognitive function, memory, speech, sleep and even the neurological decline that occurs in older adults with the disorder.
Scientists at Stanford University Medical Center already have identified abnormalities in the nerve cell structure of people with Down syndrome, differences that appear to be responsible for much of the brain damage that is the hallmark of the disorder. They’re now trying to home in on the genes that cause that particular abnormality.
“People thought that once you’re born with Down syndrome, that’s it; you can’t make the brain better. But we know that is not true about brains,” says Dr. William Mobley, a pediatric neurologist at Lucile Packard Children’s Hospital at Stanford. “Brains are plastic. We may not be able to cure this disease, but we may be able to make people’s lives better.”
Several advances have paved the way for this hypothesis. Scientists understand the brain far better than they did even 15 years ago, because sophisticated imaging devices have allowed them to better examine its structure, and the mapping of the human genome provided detailed information on the 21st chromosome. Down syndrome is caused by a third, or extra, copy of this chromosome.
The mapping of chromosome 21 revealed that it is the smallest of the 24 human chromosomes, containing about 225 genes. Now scientists such as Mobley, director of the new center for Down syndrome research at Stanford, are working to identify what those genes do.
Experiments on Down syndrome mice have shown abnormalities in the synapses, or circuits, between nerve cells. The abnormal structure and function of the synapses lead to the kind of brain damage seen in Down syndrome and Alzheimer’s disease. People with Down syndrome typically develop Alzheimer’s disease in adulthood, Mobley says.
Now researchers are trying to figure out which of the genes cause this problem in Down syndrome. Fixing the defect may involve turning off the extra copy of certain genes.
“We definitely know that genes cause this,” Mobley says. “If we find an offending gene, theoretically we can make things better by turning off that third copy.”
Treating a condition caused by an extra gene, he says, may prove easier than treating other genetic diseases such as cystic fibrosis, in which genes are abnormal or missing. Drugs could be developed to turn off that extra gene and improve cognitive ability in people with Down syndrome. Theoretically, Mobley says, the drugs could be given at any point in the lifespan to improve brain function.
“What they’re doing is extremely exciting,” says Myra Madnick, executive director of the National Down Syndrome Society. “The whole research scene has changed dramatically since the mapping of the 21st chromosome.”
Scientists caution that potential treatments resulting from this research are at least a decade away. But ultimately, Madnick says, “the result is going to be an individual who is much more independent, has a job, has an apartment, is a taxpayer. It’s not only going to enhance their lives, it’s going to enhance society.”
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About the syndrome
* Down syndrome is a genetic condition that delays physical and intellectual development. About 40% of people with the condition have congenital heart defects.
* The disorder occurs in about one in 800 births.
* Down syndrome affects all races and ethnicities.
* The incidence of the disorder increases with advancing maternal age.
* Most people with Down syndrome lead healthy lives. The average life expectancy is 55.
* Many people with the disorder can attend school and hold jobs in a supportive environment.
Source: National Assn. for Down Syndrome
