Breakthrough in Down's syndrome researchWednesday 17 July 2013 18.38
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.
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 syndrome, as well as a multitude of health problems and shortened life span.
Researchers in the US have now demonstrated a way to silence the extra 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 syndrome 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.
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 syndrome.
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.