MARLBOROUGH, Mass. — It’s not a cure for Down syndrome, but if a new drug called RG1662 works on people with Down’s as well as it has on mice, it could bring significant improvement to their thinking and learning and their chance for an independent lifestyle.

Life itself is at stake: While one in 800 children born in the United States has Down syndrome, when parents discover their child has Down’s in the womb, 90% opt for abortion.

Already, the trial drug has improved the ability of mice with Down’s to find, and then remember, their way through mazes. Further tests on humans unaffected by Down syndrome have indicated the drug has no side effects, so Swiss pharmaceutical giant Roche has moved onto clinical trials with adults with the genetic disorder.

While their primary purpose will be to retest for “safety and tolerability,” the secondary intent is to see if memory, thinking and learning are improved. If the results are positive, far more extensive tests will ensue.

A cautious Roche spokesman, neuroscientist Dr. Luca Santarelli, said in a statement, “Our drug may offer a novel therapeutic avenue to treat the cognitive deficits in people with Down syndrome, enhance their communications skills and ultimately help them have greater independence in their daily lives.”

More forthcoming was Patricia Hanbury, director of program services at the Down Syndrome Research Center in Vancouver. “It’s very exciting for us,” she said. “As a parent, I know that we all want our children to live independently and even to function in the workplace. So if this drug can improve their abilities to learn and to remember, it would go a long way in that direction.”

As well, said Hanbury, adults with Down syndrome age earlier than others, with Alzheimer’s disease a special risk. “This treatment improves memory, so there’s always a possibility the research that goes into it and how it works will uncover why Alzheimer’s happens, not only for DS people, but for everyone.”

 

Treatment Strategy

RG 1662 is the first fruit of a strategy championed by the U.S. sister organization to Hanbury’s, the Marlborough, Mass.-based Down Syndrome Research and Treatment Foundation (DSTRF). Founded in 2004, the foundation focused on identifying symptoms that had biochemical causes and which, therefore, would readily respond to drug treatments.

Down syndrome is caused at conception when three copies of chromosome 21 are transmitted from the parents instead of the usual one apiece from each parent, along with an extra 100 genes. These extra genes cause over- or under-functioning in the brain.

Since the brain regulates many thought processes by balancing “excitory” and “inhibitory” functions, too much of the second function impairs thinking. It is hoped that RG1662 will thwart the inhibitor function in humans, as it has done in mice.

But RG 1662 is just the tip of the iceberg, said Michael Harpold, DSRTF’s chief scientific officer. It is the first product of an explosion of Down syndrome research in the past five years and expected to produce other treatments shortly. “This is no longer a dream, no longer a hope,” said Harpold. “It is a reality, the first of many lines of research into ways to improve cognition for people with Down syndrome.”

Harpold added that no single “silver bullet” can explain the rapid development of treatments over the past five years. “It’s a convergence of many things.”

One step was the completion of the Human Genome Project in 2000, which, in its early stages, identified Chromosome 21 as being responsible for DS. Another was the dawning realization in neuroscience over the past 20 years that “the brain is incredibly plastic,” which means that genetic or congenital brain damage is theoretically reparable.

Nor has it hurt that “Big Pharma” has shown a surprising interest in Down syndrome, perhaps because there might be spin-off medicines for other conditions, especially Alzheimer’s disease.

“People with DS people the pathologies associated with Alzheimer’s about 20 years earlier than the general population; and, by (age) 65, at least 75% will have it,” said Harpold. He added that Roche’s clinical trial targets young adults who aren’t showing any signs of Alzheimer’s yet, but he did not rule out RG 1662’s use for Alzheimer’s in the future.

 

Targeted Abortion

But as hopes rise for Down syndrome treatment, fewer people with Down’s are being born — because of prenatal testing and targeted abortion.

According to Brian Skotko of Boston Children’s Hospital, the U.S. should have seen a 34% increase in the number of babies born annually with Down syndrome between 1989 and 2005, given the overall growth in the population.

But because of the increasing recourse to prenatal testing and subsequent abortion of nine in 10 unborn children with Down’s, there has instead been a 49% decrease in children with Down syndrome born each year.

“This is horrific,” said Janne Myrdal, head of the North Dakota branch of Concerned Women for America. “It speaks of a society going in the wrong direction.”  

Her organization was at the center of the successful campaign to get that state to ban abortion either for gender or genetic abnormalities, resulting in a law that was proclaimed last month.

In Myrdal’s view, “Down syndrome people are Providential. As one of our legislators put it, ‘They hug harder; they laugh louder; the love deeper.’”

Aborting such children, said Myrdal, “takes us back to the attitude of the 1930s, when people who didn’t measure up were seen as discardable. Abortion of DS children is just a different form of discrimination or stigmatization.”

Perhaps, suggests Janice Shaw Crouse, a senior fellow at the Beverly LaHaye Institute, the think tank for  Concerned Women for America, “the hope RG 1662 offers will keep parents from aborting their DS children.”

Added Crouse, “And perhaps, too, it will enable those precious Down syndrome children to function at higher levels and enrich the joy that almost all parents say their Down syndrome children bring into their lives.”

Register correspondent Steve Weatherbe writes from Victoria, British Columbia.