• @Aurenkin@sh.itjust.works
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    19 days ago

    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.

    • AmidFuror
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      6119 days ago

      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.

    • Atelopus-zeteki
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      2719 days ago

      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.

  • Atelopus-zeteki
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    19 days ago

    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.

  • @Potatisen@lemmy.world
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    2219 days ago

    *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.*

  • @flop_leash_973@lemmy.world
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    1519 days ago

    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.

  • Mocking Moniker
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    1219 days ago

    My heart to those who suffer. It’s so easy to underestimate the suffering of those who have digestive diseases.

    • @Eyck_of_denesle@lemmy.zip
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      418 days ago

      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.

      • Mocking Moniker
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        218 days ago

        Oh, that’s horrible. I knew a woman who damaged her esophagus and will have issues. Digestive issues are horrible.

  • @EnderMB@lemmy.world
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    519 days ago

    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.

    • @jqubed@lemmy.world
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      418 days ago

      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.

      • @AA5B@lemmy.world
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        118 days ago

        But presumably just the symptoms, right? Not the cause. So you’d be more comfortable while your immune system destroys your digestive system

        • @HeyThisIsntTheYMCA@lemmy.world
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          218 days ago

          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.

  • Lad
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    519 days ago

    I love her surname “Golightly”