Down's syndrome cells 'fixed' in first step towards chromosome therapy

Researchers shut down the extra chromosome responsible for Down's syndrome, paving the way for future treatments

Scientists have corrected the genetic fault that causes Down's syndrome – albeit in isolated cells – raising the prospect of a radical therapy for the disorder.

In an elegant series of experiments, US researchers took cells from people with DS and silenced the extra chromosome that causes the condition. A treatment based on the work remains a distant hope, but scientists in the field said the feat was the first major step towards a "chromosome therapy" for Down's syndrome.

"This is a real technical breakthrough. It opens up whole new avenues of research," said Elizabeth Fisher, professor of neurogenetics at UCL, who was not involved in the study. "This is really the first sniff we've had of anything to do with gene therapy for Down's syndrome."

Around 750 babies are born with DS in Britain each year while globally between one in a 1000 and one in 1100 births are DS babies. Most experience learning difficulties.

Despite advances in medical care that allow most to live well into middle age, those who have the disorder are at risk of heart defects, bowel and blood disorders, and thyroid problems.

Though a full treatment is still many years off, the work will drive the search for therapies that improve common symptoms of DS, from immune and gastrointestinal problems, to childhood leukaemia and early-onset dementia.

"This will accelerate our understanding of the cellular defects in Down's syndrome and whether they can be treated with certain drugs," said Jeanne Lawrence, who led the team at the University of Massachusetts.

"The long-range possibility – and it's an uncertain possibility – is a chromosome therapy for Down's syndrome. But that is 10 years or more away. I don't want to get people's hopes up."

In a healthy person, almost every cell in the body carries 23 pairs of chromosomes, which hold nearly all of the genes needed for human life. But glitches in the early embryo can sometimes leave babies with too many chromosomes. Down's syndrome arises when cells have an extra copy of chromosome 21.

Lawrence's team used "genome editing", a procedure that allows DNA to be cut and pasted, to drop a gene called XIST into the extra chromosome in cells taken from people with Down's syndrome.

Once in place, the gene caused a buildup of a version of a molecule called RNA, which coated the extra chromosome and ultimately shut it down.

Previous studies found that the XIST gene is crucial for normal human development. Sex is determined by the combination of X and Y chromosomes a person inherits: men are XY, and women are XX. The XIST gene sits on the X chromosome, but is only active in women. When it switches on, it silences the second X chromosome.

Lawrence's work shows that the gene can shut down other chromosomes too, a finding that paves the way for treating a range of other "trisomy" disorders, such as Edward syndrome and Patau syndrome, caused by extra copies of chromosomes 18 and 13 respectively.

Writing in the journal Nature, the team describes how cells corrected for an extra chromosome 21 grew better, and developed more swiftly into early-stage brain cells. The work, the researchers write, "surmounts the major first step towards potential development of chromosome therapy".

The work is already helping scientists to tease apart how an extra chromosome 21 causes a raft of problems that strike people with Down's syndrome at various ages. "By the time people with Down's syndrome are in their 60s, about 60% will succumb to dementia. One question is, if we could turn off the extra chromosome in adults, would that stop or ameliorate their dementia?" said Fisher. Another approach would cut the risk of leukaemia by silencing the extra chromosome in bone marrow cells.

The US team has already begun work that aims to prevent Down's syndrome in mice, by silencing the extra chromosome 21 in early-stage embryos. "That would correct the whole mouse, but it's not really practical in humans," said Lawrence.

A chromosome therapy for humans would be fraught with practical and ethical difficulties. To prevent Down's syndrome, the genome editing would have to be performed on an embryo or foetus in the womb, and correct most, if not all, of the future child's cells. That is far beyond what is possible, or allowed, today.

Contributor

Ian Sample, science correspondent

The GuardianTramp

Related Content

Researchers devise safer Down's syndrome test

If successful it would eliminate the small risk to the foetus posed by invasive testing methods

David Pallister

06, Oct, 2008 @11:01 PM

Article image
Are three-parent babies the first step towards a Blade Runner future? | Zoe Williams

Zoe Williams: Debate of the day: Mitochondrial transfer isn't necessarily part of the pro-choice package. It has ethical implications worth thinking about

Zoe Williams

28, Jun, 2013 @11:09 AM

Article image
Doctors develop 'transformational' new DNA test for Down's syndrome
New test more accurate than current screening in detecting Down’s, Edwards and Patau syndromes and could simplify screening process, say researchers

Ian Sample Science editor

09, Nov, 2017 @6:30 AM

Article image
Could Down's syndrome point the way to preventing Alzheimer's disease?

People with Down's are dramatically more prone to Alzheimer's than other adults. Now, scientists have united in a bid to pin down why – and to find drugs that could halt dementia. Robin McKie reports

Robin McKie

13, Oct, 2012 @11:04 PM

Bad science: How BBC misread the evidence on Down's syndrome

Ben Goldacre: Newspapers quote Radio 4 documentary presented by Felicity Finch whose founding premise was wrong

Ben Goldacre

29, Nov, 2008 @12:01 AM

Article image
Simple blood test for Down's syndrome is on its way, say scientists

Announcement made by researchers looking to replace current risky procedure that causes 1% of women tested to miscarry

Ian Sample, science correspondent

06, Mar, 2011 @6:00 PM

Genetic map of cancer reveals trails of mutation that lead to disease

Map shows how 20 patterns of mutation drive 30 cancer types, pointing the way to prevention and treatment strategies

Ian Sample, science correspondent

14, Aug, 2013 @5:00 PM

Chromosome transplant in mice could provide clue to Down's syndrome illnesses
Scientists have successfully transplanted human chromosomes into mice, a first that promises to transform medical research into the genetic causes of disease.

Ian Sample, science correspondent

23, Sep, 2005 @5:53 PM

Article image
Sleeping less than six hours a night skews activity of hundreds of genes
Genes affected by lack of sleep include those governing the immune system, metabolism and the body's response to stress

Ian Sample, science correspondent

25, Feb, 2013 @8:00 PM

Article image
Genomes project publishes inventory of human genetic variation
DNA sequences made freely available by the 1,000 Genomes Project will be used to uncover the genetic roots of disease

Alok Jha, science correspondent

31, Oct, 2012 @6:00 PM