New studies are raising the hope of finding a pill to improve the intellectual abilities of people with Down syndrome.
One study, published online by the journal Translational Psychiatry, is the first ever to show that a drug might improve the verbal memory of people with the disorder. Although the benefits appeared modest and the study was small, Down syndrome experts meeting last week in Washington called it a major development after more than a decade of research in mice and test tubes.
“A lot of us are well aware of progress we’ve seen . . . in the past five to 10 years,” said Jamie Edgin, a developmental psychologist at the University of Arizona in Tucson. Among those advances, she said, are tests designed to measure the cognitive abilities of people with Down syndrome. The development of mice with the genetic equivalent of Down syndrome, essential for studies of possible drug treatments, has been another milestone. “There’s a lot of excitement,” Edgin said.
The drug used in the recent study, Namenda, is approved for treating Alzheimer’s disease. Although it has shown only a slim and temporary benefit for that condition, a 2007 study of mice with the genetic equivalent of Down syndrome showed that it almost entirely normalized their ability to learn and remember.
The effects in humans appeared far less striking. Alberto Costa, a physician and neuroscientist at the University of Colorado in Denver, ran a test involving 42 young adults with Down syndrome, half of whom received a placebo.
After 16 weeks, most of the people who received Namenda performed better on tests of memory than they had at the beginning of the study. But the effect was statistically significant on only one of the 14 tests, which some researchers at last week’s meeting said they considered disappointing.
“It was a small improvement on a single measure,” Costa, who began studing Down syndrome after his daughter was born with it, acknowledged. “But it’s the first time in this business anybody saw anything. You can see it as a little study that had a little tiny effect, or as one of the greatest findings in Down syndrome over the past 10 years. Both are true.”
His trial was funded by the maker of Namenda, Forest Laboratories, and by the National Institutes of Health, the Linda Crnic Institute for Down Syndrome at the University of Colorado and the Coleman Institute for Cognitive Disabilities.
While he and others emphasized that it is far too early to consider offering Namenda to people with Down syndrome, Costa said he is hoping to organize another, a larger study of the drug. He also wants to test it in people with Down syndrome younger than 18.
The Centers for Disease Control and Prevention estimates that between 2004 and 2006 about one in every 700 infants born in the United States had Down syndrome, the most common genetic cause of cognitive impairment. The disorder occurs when an embryo is conceived with three copies of chromosome 21 instead of the usual two. The extra copies of all the 500 or so genes on that chromosome result in numerous physical and intellectual deficits, as well as some surprising strengths.
Individuals with the disorder are often socially outgoing. Occasionally, they develop solid tumors, cardiovascular disease or Type 2 diabetes. But they often have problems with vision, hearing, digestion and sleep apnea, and have a greatly increased risk of developing Alzheimer’s disease as they age. Their IQ averages around 50, though it can vary widely.
As hundreds of people with Down syndrome and their relatives walked the halls of the Marriott Wardman Park Hotel at the 40th annual meeting of National Down Syndrome Congress last week, the largest gathering of its kind for families, Costa and other researchers met to discuss the latest scientific findings.
The other drug being tested, known only as RG1662, is not approved for any use by the Food and Drug Administration. Roche, the pharmaceutical giant, has completed animal studies of the drug and is now running a randomized trial comparing it with a placebo on 33 young adults with Down syndrome. The primary goal of the study is to demonstrate safety, but it will also look for any sign that the drug might be improving memory.
The first 11 participants in the study have completed their testing, with no sign of dangerous side effects and a hint of possible benefit, said Julie Hoover-Fong, a clinical geneticist at Johns Hopkins University. But the full study will have to be completed before any certain conclusions can be reached, she said.
Ultimately, said Edgin, the main goal is to help people with Down syndrome achieve greater independence.
“Many parents say that more language abilities and independence is what they want for their kids with Down syndrome,” she said. “Their stress is less about IQ per se and more about their activities of daily living.”
Hurley is a medical journalist specializing in neuroscience. He is writing a book about intelligence.