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17/07/2013 16:01 BST | Updated 18/07/2013 16:40 BST

Down's Syndrome Could Be 'Switched Off' Say Scientists

A way to "switch off" the genetic defect responsible for Down's syndrome has been developed by scientists.

The technique has only been tried on laboratory cell cultures but researchers hope it could pave the way for a new form of "chromosomal therapy".

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A leading scientist questioned whether or not there was a need to find a 'cure' for Down's Syndrome

Children with Down's syndrome are born with three copies of a particular DNA package rather than the usual two.

The extra version of chromosome 21 leads to the characteristic physical appearance associated with Down's, as well as a multitude of health problems and shortened life span.

Correcting Down's with gene therapy has been too great a challenge for scientists even to contemplate.

But now researchers in the US have demonstrated a way to silence the whole unwanted chromosome, turning off hundreds of genes at once and removing the root cause of the disorder.

They did it by harnessing a naturally occurring chromosome "off switch", the XIST gene. XIST normally has the job of silencing one of the two X chromosomes in female cells. In this way, X chromosome activity in women matches that of men, who only have one X chromosome.

The scientists first created "induced" stem cells from skin cells donated by Down's patients, each of which contained three copies of chromosome 21 in its nucleus.

By inserting the XIST gene into a specific location in one copy of chromosome 21, they were able to deactivate it. Gene activity from chromosome 21 then returned to normal.

The team, whose findings are published in the journal Nature, remain cautious about where the research might lead. But the scientists plan to see if the technique can be used to correct Down's syndrome defects in mice.

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Lead author Professor Jeanne Lawrence, from the University of Massachusetts in Boston, said: "The last decade has seen great advances in efforts to correct single-gene disorders, beginning with cells in vitro (in the laboratory) and in several cases advancing to in vivo and clinical trials.

"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."

In the short-term, the technique could provide a valuable research tool for studying the process of gene silencing and underlying causes of disorders such as Down's.

But Prof Lawerence said despite the challenges it was worth pursuing the goal of regulating chromosomal activity.

"Since therapeutic strategies for common chromosomal abnormalities like Down syndrome have received too little attention for too long, for the sake of millions of patients and their families across the US and the world, we ought to try," she said.

Neurogeneticist Dr Lucy Raymond, from Cambridge University, said: "This is an exciting breakthrough, but this process is still at a very early (cellular) stage and we are nowhere near seeing this procedure being used in the treatment of Down's syndrome in people.

"This new study could, however, lead to extremely useful further studies looking at which particular genes on chromosome 21 cause certain aspects of Down's syndrome, and which might therefore be good targets for therapeutic agents."

Professor Neil Brockdorff, from Oxford University, said: "The breakthrough shouldn't be viewed as heralding a cure for Down's syndrome. This is because Down's is a sporadic disorder that affects normal development of several tissues of the foetus. There is no way of knowing in advance which embryos could be affected, and by the time diagnosis has been made, it wouldn't be possible to intervene in a holistic sense, correcting the genetic imbalance in all cells of the foetus or newborn child.

"It is worth considering that Down's syndrome patients and their families may argue that there is no need for a cure. Affected individuals generally have a good quality of life, reasonable longevity and are nearly always treasured and very loved members of their families."