19th July 2013

Down syndrome breakthrough

A naturally occurring X chromosome “off switch” can be rerouted to neutralise the extra chromosome responsible for Down syndrome, a genetic disorder characterised by cognitive impairment.

This discovery, made at the University of Massachusetts Medical School, provides the first evidence that the underlying genetic defect responsible for Down syndrome can be suppressed in cells in culture (in vitro). This paves the way for researchers to study the cell pathologies and identify genome-wide pathways implicated in the disorder – a goal that has so far proven elusive. Doing so will improve scientists’ understanding of the basic biology underlying Down syndrome and may one day help to establish potential therapeutic targets for future therapies.

“The last decade has seen great advances in efforts to correct single-gene disorders, beginning with cells in vitro and in several cases advancing to in vivo and clinical trials,” said lead author Jeanne Lawrence, PhD, professor of cell & developmental biology. “By contrast, genetic correction of hundreds of genes across an entire extra chromosome has remained outside the realm of possibility. Our hope is that for individuals living with Down syndrome, this proof-of-principal opens up multiple exciting new avenues for studying the disorder now, and brings into the realm of consideration research on the concept of 'chromosome therapy' in the future.”

Harnessing the power of an RNA gene called XIST – normally responsible for turning off one of the two X chromosomes found in female mammals – Lawrence and her colleagues showed that the extra copy of chromosomes 21 responsible for Down syndrome can be silenced in the laboratory using patient-derived stem cells. Details of their study were published this week in Nature.

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