Down Syndrome Treatment Possible


Scientists have found evidence that boosting the level of a brain neurotransmitter called norepinephrine may improve cognition in Down syndrome. The new study was conducted in mice engineered to mimic Down syndrome and suggests a new approach to treating the defects of the syndrome with medication.

Children who are born with Down syndrome are not developmentally delayed at birth, but the memory deficit associated with the condition makes it difficult for these children to gather and modulate information in a way that is necessary for normal cognitive development. Early intervention may make it possible to change this scenario and lead to an improvement in cognitive functioning.

Down syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21. One in every 733 babies is born with the syndrome, and there are more than 400,000 people in the United States living with the condition. People who have Down syndrome have great difficulty using spatial and contextual information to form new memories, a function that relies on the hippocampus. They have trouble learning to navigate complex environments, such as a shopping mall, but they are better at remembering information that is associated with sensory clues, such as colors or sounds, because these are coordinated by a different area of the brain. They also have an increased risk for congenital heart defects, hearing problems, thyroid and respiratory conditions, and Alzheimer’s disease.


Normally, hippocampal neurons receive norepinephrine (a substance nerve cells use to communicate with each other) from neurons in the locus coeruleus when contextual or relationship memories are formed. Researchers from the Stanford University School of Medicine and Lucile Packaged Children’s Hospital found that the locus coeruleus in the Down syndrome mice experienced early deterioration, as it does in humans with the condition. When the locus coeruleus degenerated in the mice, the animals were unable to perform simple tasks that required them to be aware of changes in their environment, while control mice had no problem performing.

When the researchers gave norepinephrine precursors to the Down syndrome mice, however, they were able to perform cognitive tests within a few hours after they got the drugs. They then examined the neurons in the hippocampus of the altered mice and found that these cells had responded well to norepinephrine. While the response by the Down syndrome mice was fast, the effect of the drugs also wore off relatively quickly.

Previous studies of drug treatments for Down syndrome have focused on the neurotransmitter acetylcholine, which also acts at the hippocampus. Based on these new findings, the researchers note that the ideal treatment approach for improving cognition in Down syndrome will likely enhance both norepinephrine and acetylcholine signaling.

The findings of the new study provide the first direct link between locus coeruleus deterioration in Down syndrome and a specific gene. They also provide “a ray of hope and optimism for the Down syndrome community for the future,” noted Melanie Manning, MD, director of the Center for Down Syndrome at Lucile Packard Children’s Hospital. Manning, who was not part of the research team, also noted that “We still have a long way to go, but these are very interesting results.”

National Down Syndrome Society
Stanford University School of Medicine news release Nov. 18, 2009