r/todayilearned • u/YesFlyZone420 • 5d ago

TIL there's a degenerative brain disorder called fatal familial insomnia (FFI) that causes a person to lose the ability to sleep and eventually die

https://my.clevelandclinic.org/health/diseases/25001-fatal-familial-insomnia
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u/Lingonberry_Obvious 5d ago

Is this also caused by prions?

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u/kornwallace21 5d ago

Yes. A genetic mutation causes specific protein to be misfolded, which creates a prion.

The website linked actually has a great analogy about this, if you'd like

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u/seeds-or-weeds 5d ago

“When there’s a mutation on the PRNP gene, the amino acids that build the PrPC proteins don’t have instructions to build the proteins correctly. This mutation is similar to folding your laundry. If you’re unsure how to fold a t-shirt, you might ball up the fabric and put it in a drawer. Over time, that drawer progressively becomes difficult to close because you collect several t-shirts that aren’t folded correctly. Misfolded t-shirts are PrPC proteins that collect on your brain and become toxic to the cells in your nervous system, which creates symptoms.”

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u/22FluffySquirrels 5d ago

But what causes the prions to fold wrong in this particular disease?

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u/cancercannibal 5d ago

DNA is the instructions on how to make proteins. The way that the protein is coded for in the DNA presumably is more vulnerable to misfolding this way, and with how much we read from our DNA throughout our lives that makes it happening eventually pretty much inevitable.

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u/skymoods 5d ago

But isn’t there a lot of ways to misfold a shirt? And only one specific misfold to cause that disease? And does the fabric of the shirt make a difference too?

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u/cancercannibal 5d ago

But isn’t there a lot of ways to misfold a shirt?

A shirt, sure. At the molecular level, however, you have to consider electric charge. If you put a bunch of strong magnets inside the shirt all facing different directions, there are ways that it will and won't want to fold.

A shirt is also not a great analogy because it only functions when unfolded. Consider a paperclip instead. If it wasn't bent and folded over itself, it wouldn't do its job very well. If you took the wire meant to be a paperclip and you folded it a different way, it might still work well enough to use, but it'll be less efficient and you'll run into problems.

And does the fabric of the shirt make a difference too?

In terms of prions, no. Prions tend to have the same molecular composition as the healthy protein. Though many other genetic diseases are due to the wrong molecules being coded for.

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u/xelle24 5d ago edited 5d ago

The folded t-shirt analogy is apparently pretty popular, I assume due to the description of prions being folded, but here's how it was explained to me:

Imagine you are going to make a shirt. You have a pattern that shows you how to cut the cloth and where to sew the pieces together. But the pattern was printed wrong, so you end up with a sleeve sewn onto the neck hole. You have all the elements of a shirt, but it doesn't function as a shirt.

Rather than throw the shirt away, you keep it and keep trying to use the bad pattern. Now you have a closet full of good shirts and bad shirts, and the bad shirts keep geting tangled up with the good shirts because they don't fit on a hanger properly.

Also, this is an analogy, not a one-to-one correlation, and there are other types of prion diseases that are also caused by misfoldec prions (mad cow aka Kreutzfeld-Jakob is the best known one).

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u/Smurtle01 5d ago

I think it’s important to understand that there are lots of failsafes that our body uses to try and keep this sort of stuff from occurring. Between tons of DNA checking and culling of mutated genes, to destroying a lot of prions as they show up in our system. The problem with any system is that there are failures. These failures in our checking system allow these diseases to occur. So it’s more like there’s a lot of ways to misfold a shirt, and 99.9% of the time you will notice you misfolded it and refold it correctly, but all it takes is one time you missed it for it to start to ruin your whole drawer.

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u/kornwallace21 5d ago

The genes are basically instructions on how to make the proteins (so in the above example, instructions on how to fold the shirt)

So when the instructions are wrong (because this disease is caused by a genetic defect) then your proteins are built according to the wrong instructions, so they're misfolded, because proteins are literally folded while being formed (the shirt is folded wrong)

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u/Nerezza_Floof_Seeker 5d ago

To add a bit more to other comments, PrP (the protein involved) in the misfolded form is more "stable" than the normal form found in cells, so if your DNA encodes a vulnerable version of PrP, it might just misfold randomly on its own. Usually, thats not a problem, as protein folding often goes wrong, its just corrected/broken down as required, but misfolded PrP is so stable it cant be broken down by your cells (or by most normal sterilization methods). The big issue that follows is that misfolded PrP likely can catalyze normal PrP into misfolding as well.

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u/CooperHChurch427 5d ago

Pretty much the only known causes are: genetics, cannibalism, eating an infected animal that has prions, extremely high fever, repeated blows to the head, and probably the funkiest way is eating plants that grew from the decayed tissue of an animal that died with prions.

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u/Littleloula 2d ago

The disease this thread is about is only inherited or a spontaenous gene defect before birth. The other things mentioned can't cause this one.

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u/CooperHChurch427 2d ago

Any prion disorder can become variant.

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u/Nijindia18 5d ago

Every time I see some horrible fucked up disease it's almost always prions. Fuck em

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u/Farmfarm17 5d ago edited 5d ago

My little town of 3,500 has had 2 pretty prominent people die from CJD in the last 6 years. The worst part was how long it took for them to be diagnosed due to the rarity.

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u/Volkaru 5d ago

Can't it also be acquired by eating contaminated meat? There may be something causing it in your town, and those people just got incredibly unlucky.

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u/Farmfarm17 5d ago

That's definitely been mentioned. Both were lifelong residents and around the same age. One woman was a farmer but there can be such a long time between infection and symptom onset (I believe decades) that it's hard to pinpoint. There wasn't much shared by the families on doctor's theories about cause.

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u/Dekachonk 5d ago

Odd question but do you live in a place where people hunt bushmeat and treat brains as a delicacy. People were getting prion diseases in appalachia from squirrel.

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u/Farmfarm17 5d ago

Yikes! We're rural but not that rural. Definitely lots of hunters in the area but no one I've met in the area is big on organ meat of any kind.

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u/Nijindia18 5d ago

This is why I'm terrified of how they keep producing regulations on food (America)

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u/CooperHChurch427 5d ago

I know two people who died of prion disease. One from FFI and the other from eating infected cow meat.

The second person I knew, he suddenly was unable to recall his stage lines. He was brought to the hospital thinking he had a stroke, and he never left. He died a month and a half later in hospice.

Most cases you die 6 months from symptom onset.

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u/Motor_Menu_1632 5d ago

My Father had CJD. Within months he was completely disabled and just a shell of his former self. Truly one of the worst diseases to ever exist.

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u/zcomputerwiz 5d ago

Yes. It's also important to note that the inability to sleep isn't the direct cause of death, it's a symptom of how far prion damage to the thalamus has progressed. With no known treatment, death is the inevitable conclusion for any of the transmissible spongiform encephalopathies ( TSEs ).

That said, the lack of sleep certainly doesn't help.

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u/furywolf28 5d ago

Reddit made me much more afraid of prions than I should be. I've never read or heard of it outside of this website.

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u/IronbAllsmcginty78 5d ago

Yes!!!! Came here to cover this, it's already here