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July 18, 2013

Down syndrome's extra chromosome silenced in lab cells

(Continued)

The scientists used skin cells from a Down syndrome patient that had been tricked into reverting into stem cells that, like embryonic ones, can grow into any type of tissue. Then they inserted a copy of Xist into the extra chromosome using technology from Richmond, California-based Sangamo.

Once inserted into the stem cells, scientists switched on Xist using the antibiotic tetracycline, setting off a process that effectively silenced the extra chromosome, Lawrence said.

When the chromosome had been silenced, the cells grew better in the culture, Lawrence said. What's more, they saw an increased rate of formation of cells that are precursors to neurons.

The most immediate application for the discovery is to learn about how the extra chromosome affects the development of cells, said Lawrence.

"We do hope that over the longer term, the idea of chromosome therapy could be applied to some aspects of the disease," she said. That's more than a decade away, she said. Because the technique wouldn't work in all the cells of the body, gene therapy based on this work could only be used for targeted effects, such as lowering the risk of blood cancers. Even a gene therapy for Down syndrome wouldn't necessarily be a cure, she said.

Physical issues that accompany Down syndrome include heart defects, stomach trouble, hearing difficulties and a higher likelihood of childhood leukemia. Alzheimer's disease is also very common among patients with the disorder. About 80 percent of people with Down syndrome acquire the dementia, due to the extra copy of a gene that boosts the formation of characteristics of Alzheimer's plaques in the brain.

"Down syndrome is underfunded," Lawrence said. "We're hoping what we've done here will accelerate multiple avenues of research, and maybe give more hope to the community."

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