"...prions are not an infectious entity; they’re an infectious shape."

January 15, 2019 10:15 AM

“You really want to hope that you’re negative, but the fear that you’re positive keeps interrupting, and it’s a constant psychological dialog,” she says. “Once you know, you start to adapt. What you can’t adapt to is something that keeps changing shape on you.”

When Sonia Vallabh lost her mother to a rare disease, she and her husband, Eric Minikel, set out to find a cure.

Toward the end of the dinner, Outkast’s “Hey Ya!” came on and Daruka slid down the chair to test her new powers of locomotion. She held her hands out and Minikel excused himself. “I’m being called to the dance floor,” he said. They spun in circles. “I asked for them to play this song at our wedding,” Vallabh said, laughing. After the song ended, she pulled out Daruka’s tropical-colored raincoat and began preparing her for the long walk home in the rain. Minikel, who had never once expressed any sentiment outside of optimism, sat back down, looked at me earnestly, and said, “Now that you’ve heard everything, do you think we’re going to make it?”

posted by VeritableSaintOfBrevity (19 comments total)

As someone not allowed to donate blood because of the possibility of Mad Cow lurking in my system, this is relevant to my interests.
posted by The otter lady at 10:34 AM on January 15, 2019 [14 favorites]

I didn't know FFI was caused by prions. That makes it sound even more horrifying for some reason.

The FFI-suffering naturopath mentioned in the article who went to astonishing lengths to manage his condition is discussed in detail here.
posted by figurant at 10:35 AM on January 15, 2019 [6 favorites]

That is an interesting and terrifying article, and the end is like suddenly being stabbed in the heart.
posted by Adridne at 10:39 AM on January 15, 2019 [3 favorites]

Oh wow, I went to school with both of these people and was just the other day saying how worrying it was that we had not received any updates from them in a while. Their decision to upend their lives and Do This Thing is always amazing to me.
posted by little cow make small moo at 11:25 AM on January 15, 2019 [9 favorites]

Talk about a selfish gene! There was a post here a while back about a women who received the only dose of a medication ever made, for a rare condition. Was it this woman? I would kind of hope so...
posted by Oyéah at 11:45 AM on January 15, 2019

Prions are one of my top five personal terrors. I used to work at a lab complex that had a lab down the hall that worked with them, and they had a hard time getting staff assistance, because people were so afraid of exposure.
posted by praemunire at 11:52 AM on January 15, 2019 [5 favorites]

In this way, kuru resembled scrapie, a fatal degenerative illness that causes sheep to obsessively scrape themselves against fences.

If you’re a professional disease namer and you phone in a bullshit name like “scrapie”, it’s time to consider a career change.
posted by dr_dank at 12:45 PM on January 15, 2019 [10 favorites]

Oh wow, what a powerful article - and such an amazing couple! I am just astounded. When my baby was diagnosed with a rare, life-threatening genetic disorder my only thought was to figure out a way to keep our health insurance as stable and comprehensive as possible (because America). That has turned into the driving force of my career, for better or worse. I did not have the mental bandwidth to dive into the science of his genes, his liver, or his lab results, and, six years later, I’ve still chosen not to go there. The fact that this couple changed the entire trajectory of their lives and their life’s work and that they have the brainpower and people-skills to make it happen... Just amazing. I wish them all the best.

And maybe my kid will grow up to research and cure his own disease. I hope Sonia survives to teach the next generation.
posted by Maarika at 2:20 PM on January 15, 2019 [7 favorites]

Previously, and a great book about FFI.
posted by Dashy at 2:38 PM on January 15, 2019

The gene for human PrP is located on chromosome 20 out near the end of the short arm. PrP is highly conserved among mammals, which probably means it's doing Important Things.

Given its affinity for Copper, Zinc, Manganese and Nickel, which are all essential for humans, those things are likely to be involved with handling metals, and the linked Wikipedia article says it also helps reduce the toxicity of heavy metals.

It would be interesting to know whether it retains its affinity for metals in its misfolded disease-inducing form, but it might be even more interesting to know whether binding to a metal ion prevents it from misfolding in the first place, because in that case a cocktail of metals might arrest the progress of FFI the way chemotherapy is supposed to for cancer.

Or if it turns out to act as a reservoir of the essential metals it has an affinity for, maybe a diet so poor in those metals as to be just barely life sustaining (and also very low in toxic heavy metals) could prevent PrP from being transcribed much at all, and limit the disease that way.
posted by jamjam at 2:44 PM on January 15, 2019 [2 favorites]

Wow, so sad, interesting and amazing at the same time. Thanks for sharing.

I have a friend whose parent died of something related to 'prions' and part of me wants me to send this to her so she can feel a sense of relating to others who have gone through something similar, and part of me also wonders if her parent's disease was genetic and my friend may be at risk (and not know). I don't know if this article landing in her inbox would be a bomb or a gift. :/
posted by Halo in reverse at 3:16 PM on January 15, 2019 [1 favorite]

There was a post here a while back about a women who received the only dose of a medication ever made, for a rare condition.

You may be thinking of this post, which is about a different disease and patient. I remember hearing about this couple on NPR a while back; I hope things go well for them.
posted by TedW at 3:16 PM on January 15, 2019 [2 favorites]

Prions are so damn creepy. What do you do about a misfolded protein that corrupts normal proteins?

Antisense oligonucleotides are pretty exciting stuff, though. I really really hope they work. I was in the meeting when Ionis (formerly known as Isis... yeah) showed videos of kids with SMA walking around and riding bikes. It was incredible.
posted by basalganglia at 3:17 PM on January 15, 2019 [2 favorites]

Prions are so damn creepy.

Oh, then don't read these articles from Derek Lowe's In the Pipeline.

Prions In the News (Unfortunately)
Type 2 Diabetes May Be a Protein Misfolding Disease
Alzheimer’s and Infectious Disease: For Real
We Have Given People Amyloid Disease
posted by ryanrs at 5:55 PM on January 15, 2019 [1 favorite]

These misfolded proteins are incredibly tenacious and are transmitted like zombie bites from prey to predator and maybe back to prey. Consequently, you'd expect them to flow through vertebrate populations in a chain reaction - but they don't! So there must be a mechanism that either refolds them, or somehow manages to exclude them. Except when it doesn't work, of course, or perhaps when it's overpowered.
posted by Joe in Australia at 8:53 PM on January 15, 2019 [1 favorite]

I think they're going to make it.
posted by From Bklyn at 2:56 AM on January 16, 2019 [1 favorite]

This is like your own personal, slow-motion Gamma-Ray Burst. Terrifying and unlikely but also without any sort of solution or protection once it happens.
posted by Godspeed.You!Black.Emperor.Penguin at 8:27 AM on January 16, 2019

Consequently, you'd expect them to flow through vertebrate populations in a chain reaction - but they don't! So there must be a mechanism that either refolds them, or somehow manages to exclude them. Except when it doesn't work, of course, or perhaps when it's overpowered.

I think that's a really good point, Joe.

Back when all this was first coming out I had a joke with a friend that there must have been a prion catastrophe somewhere in eukaryote history, where they were reproducing their little flagellae off, a seed prion suddenly appears just by chance, and foomp! a mass extinction event. And a few years later, when I read about a project to identify 'forbidden' DNA sequences, sequences which are never seen in organisms and which therefore must somehow be deadly, and translate them into protein, I wondered whether prions might show up somewhere.

And I think you're right about a mechanism which excludes them.

The Wikipedia article I linked above mentioned that the messenger RNA for prion protein, the RNA string which is polymerized directly from the DNA sequence for the protein and is then translated by a ribosome into the protein itself, contains something called a prion pseudoknot, in which the messenger RNA loops back on itself and forms a structure which is represented pictorially as a dumbbell with unbalanced weights and a handle region where RNAs some distance apart on the string are actually hydrogen bonded together.

I have no idea how a ribosome could process such a thing, but it must be exceedingly tricky, and I'd bet it functions to keep some dangerous mRNAs from being translated into protein -- but not all of them, apparently.
posted by jamjam at 12:28 AM on January 17, 2019

scrapie is one of those disease named by farmers ....
posted by mbo at 3:41 PM on January 17, 2019 [2 favorites]