Google – AFP, Richard Ingham (AFP), 17 July 2013
 |
A
geneticist looks at a chromosome analysis process at her laboratory on
October
31, 2002 (AFP/File)
|
PARIS,
France — Gene scientists on Wednesday said that in lab-dish cells, they had
found a way to switch off the rogue chromosome that causes Down's syndrome.
The
breakthrough opens up the tantalising goal of therapy for Down's, they said,
cautioning that years of work lie ahead before this aim is reached -- if, in
fact, it is attainable.
Down's
syndrome is the world's leading genetically caused mental disease, accounting
for around one in 600 live births in the United States.
It also
carries with it a heightened risk of heart defects, leukaemia, immune-system
malfunction and premature Alzheimer's disease.
The
disease, formally called trisomy 21, is caused by an additional chromosome 21,
which has a cascade of unexplained impacts on brain development and body
function.
Acting on a
hunch, scientists at the University of Massachusetts Medical School reported
that they had inserted a gene into this unwanted third chromosome and, in
effect, used it like an off switch.
It is the
first time that correction has been achieved for an entire chromosome, a coil
of DNA that is studded with hundreds of genes, the protein-making codes to
build and sustain life.
"Our
hope is that for individuals living with Down's syndrome this
proof-of-principle 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," said Jeanne Lawrence, a
professor of cell and developmental biology.
People
without Down's are born with 23 pairs of chromosomes, including two sex
chromosomes, which pair up as two X chromosomes for females and an X and Y
chromosome for males.
The team
noted that, in early female embryos, a special gene called XIST comes into
play, silencing one of the two X chromosomes so that they do not over-function.
Their bet,
published in the journal Nature, was whether XIST could be slotted into the
third, unwanted chromosome 21 in cells from a person with Down's.
The research
was carried out from so-called induced pluripotent stemcells, or cells that
have been reprogrammed to their versatile infant state.
Delighted
with the chromosome silencing they saw in a lab dish, Lawrence's team have now
started to test the technique on mice genetically modified to have trisomy 21.
The results
should be known "hopefully within a year", Lawrence said in a phone
interview with AFP.
Tests on
lab animals are an early part of the long process of assessing a new drug or
process to see if it is safe and effective for humans.
Lawrence
readily acknowledged that what happens with mice may not be the same in humans,
but said a conceptual logjam about chromosome therapy had at last been broken.
"I
think that the importance of this work is that it now makes it conceivable --
not that we know that it will work or that it won't be a long way off, because
there are a lot of questions and a lot of steps to be met," she said.
Gene
therapy aims at fixing inherited diseases by substituting flawed genes with
functioning ones.
After more
than a decade of frustrations and setbacks, this high-risk field is now coming
to fruition.
But so far,
the advances are only in diseases caused by single-gene defects, not by
multiple genes or a whole chromosome, which are far more complex, Lawrence
said.
The
greatest benefit of the work could be its contribution to a basic understanding
of how trisomy 21 disrupts cells, she said.
If
scientists can figure out at least some of the pathways, this opens up options
for drugs that can block some of the ill effects of Down's.
"There
are different severities of Down's syndrome," she said.
"There
are a lot of people with Down's syndrome who are really near the threshold of
being able to lead an independent life or hold down a job, and there are things
that may be able to help them to achieve it."
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