Researchers turn off Down’s syndrome genes

[n2doc]

by Beth Mole

The insertion of one gene can muzzle the extra copy of chromosome 21 that causes Down’s syndrome, according to a study published today in Nature1. The method could help researchers to identify the cellular pathways behind the disorder's symptoms, and to design targeted treatments.

“It’s a strategy that can be applied in multiple ways, and I think can be useful right now,” says Jeanne Lawrence, a cell biologist at the University of Massachusetts Medical School in Worcester, and the lead author of the study.

Lawrence and her team devised an approach to mimic the natural process that silences one of the two X chromosomes carried by all female mammals. Both chromosomes contain a gene called XIST (the X-inactivation gene), which, when activated, produces an RNA molecule that coats the surface of a chromosome like a blanket, blocking other genes from being expressed. In female mammals, one copy of the XIST gene is activated — silencing the X chromosome on which it resides.

Lawrence’s team spliced the XIST gene into one of the three copies of chromosome 21 in cells from a person with Down’s syndrome. The team also inserted a genetic 'switch' that allowed them to turn on XIST by dosing the cells with the antibiotic doxycycline. Doing so dampened expression of individual genes along chromosome 21 that are thought to contribute to the pervasive developmental problems that comprise Down's syndrome.

more

http://www.nature.com/news/researchers-turn-off-down-s-syndrome-genes-1.13406

[mike_c]

1. sounds like a great way to silence any trisomy extra copy...

...although as a practical matter, it's not clear how this could be done during normal development. I would think it would require very early insertion in order to incorporate the silenced copy throughout the developing embryo.

[Ilsa]

2. Kick.

[cbayer]

3. Wow! Just think of the potential implications of this.

[Squinch]

4. I am thrilled about this, but I just had a very strange reaction:

I work with a lot of kids with disabilities, and three or four faces of kids I LOVE who have Down's Syndrome just flashed in my mind. I know the condition is very difficult, but I would hate to have missed the experience of knowing those kids.

I am surprised by my own reaction.

[tavalon]

5. I'm not

My first thought was, "uh-oh, here it comes." I've known for years that I was likely to see the day when gene therapy would possibly eradicate some awful diseases but I figured the money would go into making the perfect baby. Kids with Downs are often jewels, but they are imperfect, and I fear they will become extinct. My own son has autism. I still have dreams where he doesn't, where he can talk to me normally, but then I think of all the wonderful parts of his disability, they would be gone too.

[cbayer]

6. I think there is a big difference between autism and trisomy-21 though.

Trisomy-21 is a clear genetic mistake. Prior to modern medicine, most of these children would have died. The consume enormous medical resources and often suffer unspeakable illnesses.

While I have known and loved kids with trisomy-21, I have also known and loved kids with AIDS. Knowing and loving them doesn't mean that we shouldn't try to prevent or cure their illnesses.

As women wait longer to have children, the risk of a trisomy-21 child goes up. Being able to prevent this could mean a great deal to women in general.

It's not about making them extinct or having the perfect baby. It's about eliminating a genetically based illness.

This is an entirely different kettle of fish from the autism spectrum disorders.

[Squinch]

8. But Down's Syndrome isn't an illness.

[cbayer]

9. What makes you say that? And if not, what might you call it?

[Squinch]

7. I think I'd rather see a world where we care for these kids and appreciate them, and

offer them a path to independence when they grow up.

That being said, there ARE certain genetic anomalies that are truly devastating. I'd love to see Muscular Dystrophy and Spinal Muscular Atrophy eradicated.

[cbayer]

10. Why differentiate here?

Why wouldn't you hold the same position about caring for, appreciating and offering a path to independence of people with Muscular Dystrophy or Spinal Muscular Atrophy?

[tavalon]

11. Absolutely!

I just suspect that things like Down's syndrome will be the first target instead of those truly awful genetic anomalies. There is another trisomy that is incompatible with life. I'd rather we target that.

[cbayer]

12. My 1 year old trisomy 21 nephew was just tortured in a NICU for several weeks.

This is a truly awful genetic anomaly for some kids. Just because they are often very lovable and loving does not mean they don't suffer.

[Heddi]

13. Not all people with Downs Syndrome can be independent. Many are severely disabled

My cousin has Downs Syndrome. He is profoundly disabled and will never live anything close to an independent life ever.

He recently turned 17 and is just beginning to be kind of, sort-of 'potty trained'

He is cared for by his 65 year old grandmother (my aunt), who adopted him because her daughter (his mom) was too mentally ill and drug addicted to care for him herself. The choice was for my aunt to adopt him, or have him go into institutionalization.

Along with the mental disabilities are the physical issues too. Heart problems, thyroid problems, skeletal problems, deafness and blindness are just a few of the physical issues that also plague those with Downs Syndrome.

My cousin has had to have several lengthy hospital stays because of cardiac defects/problems that are a direct result of his Downs Syndrome. These hospitalizations are always extremely stressful for Johnny because you can't explain to him an IV, or medicine, or that he has to stay in bed, or that he can't roll on the floor in the hospital. It's terrifying, he's difficult to medicate because of kidney problems, and nearly impossible to intubate because of his short, fat neck. Every time he is hospitalized there is a very great risk that he won't come out---not because he's having heart surgery, but because he's a downs syndrome boy having heart surgery.

My aunt is in her 60's. She won't live forever. WHere will Johnny go when she dies? He has the speech and cognition of a 3 year old. He will never live independently. He is prone to anxiety attacks. He does not adapt to new situations. Staying with one of my aunts other daughters is out of the question...he knows and loves them, but cannot be without my aunt because he freaks the fuck out for days. DAYS at a time, which often results in hospitalization and sedation.

His future is bleak. That's being totally realisitic. He will never live independently. He can't even be toilet trained for any length of time. His quality of life is decreased with each surgery, which gets more and more frequent the older he gets.

You say you work with the disabled...perhaps you've never seen or spent time around the profoundly retarded, those with severe forms of trisomy 21 and trisomy 18? They're not all cuddly little Corky's who are full of innocence and love. They are living tortured lives, often blind and deaf with no intellectual ability to understand or learn language such as braille or sign to understand the life they are living. They are doomed to live in nursing homes or state institutions when their primary caregivers die.

On edit: My cousin, like many of the profoundly disabled, is completely incapable of doing the following things:
- feeding himself
- toileting himself
- dressing himself
- having an intellectual capability beyond a 2-3 year old
- he cannot dial a phone
- he is difficult to understand by anyone not familiar with his speech patterns
- he cannot read

he's 17 or 18 years old now.

how will he ever reach "independence"?