[HN Gopher] Charm creates a potent therapy candidate for fatal p...
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Charm creates a potent therapy candidate for fatal prion diseases
Author : gmays
Score : 43 points
Date : 2024-07-11 19:21 UTC (3 hours ago)
(HTM) web link (news.mit.edu)
(TXT) w3m dump (news.mit.edu)
| el_benhameen wrote:
| The Wired deep dive on the couple whose lab this came from is
| worth a read: https://www.wired.com/story/sleep-no-more-crusade-
| genetic-ki...
| gushogg-blake wrote:
| Does this affect infectious prion diseases as well, or just the
| genetic ones? Article makes it sound like everyone has the prion
| protein gene, so not sure what the different etiologies are. My
| understanding was that prions were just self-replicating proteins
| with no biological mechanisms involved, but apparently it's more
| complex than that.
| Terr_ wrote:
| It sounds as if this is mostly a case where the initial
| infection is a matter of time, and the goal is to stop it from
| occurring:
|
| > CHARMs, however, work further upstream, turning off the gene
| that codes for the faulty protein so that the protein never
| gets made in the first place. [...] In a person who hasn't yet
| developed symptoms, removing the protein should prevent disease
| altogether.
|
| That said, it may still be relevant as a helpful therapy for
| someone already infected, if the accidental production of
| "fresh" prions--happening in parallel in all cells--is a much
| bigger problem than an existing prion floating around and
| catalyzing neighbors:
|
| > Testing in mice showed that ZFP-guided CHARMs could eliminate
| more than 80 percent of the prion protein in the brain, while
| previous research has shown that as little as 21 percent
| elimination can improve symptoms.
| thatoneguy wrote:
| Both the communicable and noncommunicable prion diseases still
| require a particular protein (and typically protein isoform
| since some folks are resistant to vCJD) to be present so I
| think this would work on both forms. That said, someone doesn't
| normally now they have a prion disease until it's probably too
| late to do anything about it.
| throwawaymaths wrote:
| Possibly.
|
| A corrections: a prion (the disease agent) is believed to be a
| self replicating protein fold, so it needs a source protein
| ("prion protein", aka PrP, one word) to feed the folding.
|
| Now, although the evidence is pretty solid that the fold is the
| infectious agent, there's a lot of unanswered questions: we can
| try to make prions in the lab but iiuc no one has made a fiber
| of PrP in the lab _without_ seeding from an infectious sample
| that itself was infectious.
|
| Moreover, a lot of related Alzheimer's research has come under
| intense scrutiny recently[0], so much so that the viral
| hypothesis of Alzheimer's is now dominant and no longer the
| "prion-like hypothesis", so, it's possible that the self-
| propagating protein fold is not the infectious agent for prion
| disease either.
|
| If it is, then it's likely that turnjng down PrP in the brain
| will slow or even reverse the disease. The PrP fibers
| _probably_ can be degraded, if very slowly, and turning off the
| spigot of source material for the fold will push the
| equilibrium in the other direction
|
| [0] see marc tessier levigne (current CEO of AI/biotech form
| Xaira)'s firing?resigning? from stanford due to fraudulent data
| in his lab
| oigursh wrote:
| It's believed the UK will suffer from a batch of hidden vCJD
| prion disease in the next decade or so. Well needed therapy.
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