Down Syndrome Treatment Study Shows Experimental Drug Reverses Cognitive Deficits In Mice

DOWN SYNDROME

There's still no cure for Down syndrome, but recent research is raising hopes that drugs can be found to counter the cognitive deficit that characterizes the genetic disorder.

In July, University of Massachusetts researchers said they had found a way to shut down the extra chromosome that causes the syndrome. at least in test tubes. And now comes word that scientists have identified a compound that brings dramatic improvements in learning and memory in mice bred to have a Down-like condition. One injection of the compound given on the day of birth seemed to work by allowing the animals' cerebellums to grow to full size.

"Most people with Down syndrome have a cerebellum that's about 60 percent of the normal size," Dr. Roger H. Reeves, a professor at Johns Hopkins University and one of the scientists behind the research, said in a written statement. "We treated the Down syndrome-like mice with a compound we thought might normalize the cerebellum's growth, and it worked beautifully. We were able to completely normalize growth of the cerebellum through adulthood with that single injection."

Those bigger cerebellums certainly seemed to do the trick. In subsequent tests, mice given the injection were significantly better than untreated mice at learning and remembering how to find their way while swimming in a so-called water maze.

Just what is the stuff that brings this amazing result? It's a complex organic molecule that belongs to a family of compounds known as "sonic hedgehog pathway agonists." The compounds seem to "supercharge" the action of sonic hedgehog, a "growth factor" protein

that helps regulate growth and development of body tissues.

Reeves said the molecule could eventually find use as a human drug, adding that clinical trials are already underway to evaluate other cognition-enhancing drugs in people with Down syndrome. But he said the molecule won't be ready for clinical trials until several hurdles are overcome--including making sure the compound doesn't cause cancer, uncontrolled growth, or other serious problems.

"We have to figure out the minimum doses and modes of delivery, example possible side effects and optimize timing before it could be considered as a possibility for human trials," Dr. Reeves told The Huffington Post in an email, adding that funding for such research was in short supply.

Even if the compound does become a drug, of course, it wouldn't represent a cure for Down syndrome. The condition, which results from an extra copy of chromosome 21, can cause heart trouble, bowel problems, sleep apnea, and other problems in addition to the characteristic intellectual disability and facial features.

"Down syndrome is very complex, and nobody thinks there's going to be a silver bullet that normalizes the condition," Reeves said in the statement. "Multiple approaches will be needed."

About one in every 800 babies in the U.S. is born with Down syndrome. according to the website of the Down Syndrome Research and Treatment Foundation. Worldwide, just under six million people have the condition, including about 350,000 people in the U.S.

The new research findings were published in the Sept. 4, 2013 issue of Science Translational Medicine .

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