NEW YORK — Aiming deep inside the brain, drugmakers are testing medicines that may improve learning in people with Down syndrome, an advance unimaginable 50 years ago when many children with the genetic condition were considered hopelessly disabled.
About 6,000 U.S. babies are born with Down syndrome each year. Most attend school, aided by programs designed to help them deal with their disabilities. Now Roche Holding and Balance Therapeutics, taking advantage of a research renaissance in brain science, are testing drugs in human trials that may pave the way toward a new era. The goal: Improve the ability of these children to remember and learn.
The treatments aren’t a cure, and don’t address the underlying genetic problem. Instead, they aim to compensate for chemistry imbalances inherent in the condition by boosting the ability of nerve cells in the brain to communicate and form long-lasting connections, crucial for memory formation.
“Ten years ago if you told anyone there were going to be trials of drugs to improve cognitive symptoms of Down syndrome they would have laughed you out of town,” said Roger Reeves, a geneticist at Johns Hopkins University in Baltimore. The advances “in the just last five years are truly amazing.”
Down syndrome is among the most common genetic causes of intellectual disability, afflicting 250,000 Americans. It’s caused by having a third copy of chromosome 21. The main known risk factor is maternal age, with most cases occurring randomly in egg-cell maturation or sperm formation.
Besides mild to moderate cognitive impairment, the extra chromosome can cause problems that range from heart defects to hearing problems to intestinal disorders.
Michelle Schwab, of Holly Springs, N.C., whose 16-year-old son, Matthew, has the condition, says algebra is a difficult task for him because he can’t remember the steps needed to work out the problems. Spatial tasks, such as reading an analog clock, are also difficult, Schwab said.
Matthew is a freshman in public school, according to Schwab. A drug that would help him overcome those educational hurdles as he makes his way up through high school would “be tremendous,” she said in a telephone interview.
“Because he functions so close to normally in every other area, it is frustrating to watch him struggle academically,” she said. “It would be wonderful if there were something that could enhance his cognitive ability, and just make things a little less difficult.”
Cognitive-enhancing drugs may have a significant impact, doctors say. An IQ boost of just 10 to 15 points could greatly increase the chance that someone with the syndrome would be able to live independently as an adult, said Brian Skotko, co-director of the Down syndrome program at Massachusetts General Hospital in Boston, who has a sister with the condition.
Classroom interaction
Children with the disorder benefit from federal laws that require schools to accommodate people with disabilities in regular classrooms as much as possible. Each change in the law “has improved the way students with Down syndrome are integrated into the classroom,” said Sara Weir, vice president of advocacy and affiliate relations at the National Down Syndrome Society.
Both Roche, based in Basel, Switzerland, and Balance Therapeutics, a closely held company in San Bruno, Calif., are testing drugs that counteract a chemical called GABA that depresses activity in brain cells. Lab studies suggest the extra chromosome may spur excess activity from the chemical, disrupting a crucial balance in the brain.
New technology developed in the last two decades has helped scientists dramatically increase their understanding of the sometimes subtle changes that occur within the brains of children with development disorders. They now see conditions such as Down syndrome and autism “as very specific pathologies that can be targeted with drugs,” said Omar Khwaja, a neurologist who leads Roche’s Down syndrome trials program.
A study published in February 2013 in the Journal of Neuroscience showed that one of the Roche drugs restored memory function and increased brain-cell growth in mice with Down syndrome. A human efficacy trial, set to begin within weeks, will test a related Roche compound in 180 adolescents and young adults with Down syndrome.
