Old drug may treat children with Down Syndrome - Study

Mental retardation caused by Down syndrome can be reduced by a long-discredited drug that Stanford University researchers found effective in improving the mental abilities of mice with the genetic disorder.

Researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital, whose study published on Feb. 25 in the advance online edition of Nature Neuroscience, gave low doses of human drug to mice bred to mimic the learning and memory problems in people with Down syndrome.

Merely two weeks later, the impaired mice, treated with the drug, known as pentylenetetrazole or PTZ, performed as well as normal ones in learning tests, including recognizing objects they had seen before or remembering how they last entered a T-shaped maze, the researchers found.

What's more, the improvement lasted for up to two months after the treatment was discontinued. The drug, once used to study epilepsy in animals, also might help people, the US researchers said.

"This treatment has remarkable potential," said Craig Garner, PhD, professor of psychiatry and behavioral sciences and co-director of Stanford's Down Syndrome Research Center. "So many other drugs have been tried that had no effect all. Our findings clearly open a new avenue for considering how cognitive dysfunction in individuals with Down syndrome might be treated."

However, the researchers caution that the research is preliminary and it is too early to tell if the drug will be effective in human. Researchers also strongly cautioned individuals against experimenting with the compound or taking it on their own.

The researchers are now considering a clinical trial to test whether the compound, with once-a-day, short-term treatment, has a similar effect in humans with Down syndrome. However, it can take a year or two to initiate the trials, and evaluating them might take five to 10 years, Garner said.

PTZ is not currently approved by the Food and Drug Administration (FDA) for use in humans. The US health agency in 1982 had withdrawn approval for the use of PTZ in humans because no clear clinical benefit had been established.

Although the compound is almost a century old and was used to treat psychiatric disorders and later dementia, but researchers never concluded it was effective. It also caused seizures (at doses 100-fold higher than those given to the mice), forcing the FDA to remove the drug from the markets.

Seizure is a sudden change in behavior characterized by changes in sensory perception (sense of feeling) or motor activity (movement) due to an abnormal firing of nerve cells in the brain.

The genetic disorder caused by an extra copy of the 21st chromosome, Down syndrome, is the most frequent genetic cause of mental retardation and occurs equally around the world. It occurs in one of every 733 live births.

According to the National Down Syndrome Society, more than 350,000 people in the United States have the condition, and nearly 5,000 children born in America each year have Down syndrome.

The disorder typically causes mild disability to moderate mental retardation and can increase the risk for Alzheimer's disease, leukemia and congenital heart defects.