They found a weak spot in our DNA that is present in 95% of people with the disease. It makes it much easier for some immune cells to go haywire and drive excessive inflammation in the bowels. The team have found drugs that already exist seem to reverse the disease in laboratory experiments and are now aiming for human trials.
this post was submitted on 05 Jun 2024
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The "weak spot" is an enhancer region about 290 Kbp from the gene ETS2 mentioned elsewhere in the comments. The haplotype associated with IBS leads to overepression of the gene. They did some nice cell and molecular work to confirm the enhancer's effect on the gene and the genes effect on inflammation response.
It's the woman in the thumbnail, isn't it? She's been causing it?
LOL 😂 that was my first thought. Wouldn't you love to be scientist credited for, or the stock photo model for article titles like this?
Lauren Golightly
She may not be the cause, but I hope she's making a killing off of all the colonoscopy prep sales!
Somebody stop her!
Why did I have the same reaction xD. Great minds think alike.
Five bucks says this will be more useful than for just IBD.
From the abstract: "By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3,4,5,6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. "
I guess you owe me five bucks.
What? I put money that it'd be useful for MORE than IBD. You bring evidence of what I was putting money on.
Ankilosi spondylitis is quite different than IBD.
This is exactly why I'm not a gambler. ;-) I really prefer it when people say things like, "wow, thanks, here have a fiver."
It was her all along!
A disease-associated gene desert directs macrophage inflammation through ETS2 https://www.nature.com/articles/s41586-024-07501-1
Abstract
Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3,4,5,6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.
I also saw the thumbnail and had a laugh.
"major cause found!" -- image of woman's face
She's like: "I need a new agent..."
A little chortle now and then. Keeps things from getting to 'heavy'.
lol same!
"Major cause found; Becky is at it again!"
...
*A major cause of inflammatory bowel disease (IBD) has been discovered by UK scientists.
They found a weak spot in our DNA that is present in 95% of people with the disease.
It makes it much easier for some immune cells to go haywire and drive excessive inflammation in the bowels.*
This kind of discovery is really cool to hear about.
But the impatient part of my brain really hates to read stuff like "hoping to start human trials within five years". Gotta be careful and do it right and all that. But my monkey brain wants that Star Trek medicine now where I go in with literally anything and almost all of it is curable and a lot of it with only some sort of non-evasive tool while I am young enough to benefit from it.
Misread it as "Major case" and wondered why she was so happy about it.
My heart to those who suffer. It's so easy to underestimate the suffering of those who have digestive diseases.
Idk if this is a digestive disease but my dad has stomach ulcers because of misdiagnosis of malaria. I apologise if my information is slightly flawed cause Indian parents don't share these properly. It affected him alot. He used to be really big and fit which he is still but not to an earlier extent. He also can't eat any of his fav foods.
Oh, that's horrible. I knew a woman who damaged her esophagus and will have issues. Digestive issues are horrible.
but how do I fix it, explained in dum dum level english?
They just found some commonalities in DNA, doesn’t mean they found how to fix.
Get new DNA. Or a patch.
Go to the Doctor, quick.
I love her surname "Golightly"
I wanna meet her alter ego "GoHardly"
As someone with IBS, I've kept an eye on potential remedies or cures for years, and while I'd love to be supportive of this, I'm skeptical that it will actually amount to something until human trials are effective and treatment actually starts to roll out.
From the article:
The disease is distinct from irritable bowel syndrome (or IBS) although some of the symptoms overlap.
I also have IBS, although as a diagnosis it feels more like a catch-all for when there’s clearly a problem but they’ve ruled out more serious diseases like ulcerative colitis. I have other friends with the same diagnosis as me but very clearly different triggers, symptoms, and things that help, so it seems like we really have some different diseases. That said, I’ve seen some significant improvement in the past few years thanks to a combination of medicines. Not a cure, but less bad days and flare-ups often don’t last as long. I actually saw an as the other day for a completely different medication than any I currently take, so if you haven’t talked to your gastroenterologist about treatment options since before the pandemic it might be worth checking in.
Only thing I've found what works consistently (and, yeah, I know, eyeroll here) is THC.
But presumably just the symptoms, right? Not the cause. So you’d be more comfortable while your immune system destroys your digestive system
Hard for me to tell in my specific situation. But my flareups from being exposed to trigger foods went from managed in two weeks by the shit the GI prescribed to being managed in forty five minutes to two hours by thc.
Sounds like a great improvement!
I've been through some fairly novel medical shit, so they use me in medical education a bit. I'm the local "THIS IS THE DUDE YOU WANT ON CANNABIS" guy they trot around to all the medical CPEs. It's fun.
Great!
So it's a gene that causes the immune system to overreact, but what is it overreacting to?
Thank god for these scientists!