4 ms·

What would a cure for prion diseases even look like? Are prions targeted by the immune system at all? That to me is what is scary about them.

itchyouch 9y ago
From what I recall, they are seen as normal proteins by the immune system, thus not targeted. A simple illustration on prions was to imagine it like a busted cable end that would break the socket it plugs into, then the socket would break other cable ends plugged into it. This would occur until all sockets and cable ends were broken in the same way.
- phkahler 9y ago
  Decades ago, we had a PCMCIA card that did exactly that. A bent pin distorted the plastic in the socket and that led to more bent pins. Of course you had to try to force them in to propagate the problem and we never tested to see how many generations it could last. Once discovered we threw out all defective hardware which was just a few cards by then.
  - jacobush 9y ago
    I have heard this one before!
- jandrese 9y ago
  It's the Zip Drive click of death for your body.
  - LordKano 9y ago
    I was going to make this same point.
abetusk 9y ago
Not a direct answer to your question (because I don't know) but there's a couple doing research into a cure for prion disease because one of them (Sonia Vallabh) has it. Eric Minikel has been blogging about their research [1] [2], maintains an active Twitter presence [3] and has GitHub [4] repositories on the issue. The blog has a lot of information for anyone wanting to know more about bioinformatics, basic research and prion disease in particular. [1] http://www.cureffi.org/ http://www.cureffi.org/ [2] http://www.cureffi.org/about/ http://www.cureffi.org/about/ [3] https://twitter.com/cureffi https://twitter.com/cureffi [4] https://github.com/ericminikel https://github.com/ericminikel
- dmix 9y ago
  > Sonia and I set out on a quest to re-train ourselves as scientists. We both started taking night classes, reading papers, calling up scientists, going to conferences. We left our old careers and found jobs in research labs, and eventually enrolled at Harvard Medical School, where we are now PhD students in biological and biomedical sciences. Wow, what a great story. Inspiring that you can change careers mid life and be successful. Thanks for sharing.
dllthomas 9y ago
> What would a cure for prion diseases even look like? Well, I mean, in some way the prion behaves differently than its normal counterpart. A molecule that interacted with that in such a way as to destroy the prion would seem to be a cure, right? At least, if not otherwise too harmful...
- s0rce 9y ago
  Or bind with it such that it is now inert, refolded back to a proper configuration or label it for destruction by the immune system.
- amelius 9y ago
  Or how about a molecule that binds to the harmful part of the prion?
dnautics 9y ago
If we do devlop a cure for prion diseases, short of a biofilter in a transporter beam, it will probably be some sort of directed antibody that magically only recognizes prion form of the prion protein, sequesters it and prevents spread; and maybe if we're clever at molecular engineering, also recruits the body's natural capability to clear these proteins (insulin-degrading enzyme).
scythe 9y ago
There are molecules that cause prions to "refold" back into the healthy form. The problem is that so far every such known molecule is highly toxic, e.g. guanidinium chloride.
dragonwriter 9y ago
> What would a cure for prion diseases even look like? You'd need something that responded to the physical conformation difference in the prion (which is clearly possible because prion disease is exactly a difference in behavior based on that) in a way which somehow selectively disrupts or expels the prion form of the protein (while different reaction is clearly possible, the desired difference is less clearly acheivable.) I suppose some kind of nanomachine that actually physically reconfigured proteins from the prion conformation to the healthy one might also be plausible, eventually.
- ajnin 9y ago
  The particularity of prions is that when they come into contact with the normal form of the protein, they can change its conformation to create a new prion (that's how the disease spreads). In that light I think an "anti-prion" protein should be possible, going around the body converting prions back into healthy molecules.
Cybiote 9y ago
We can look at kuru survivors who sadly, recently underwent rapid natural selection. Among this population are those possessing a variant of the prion protein gene that conveys strong resistance to prion diseases and the propogation of misfolded prion proteins. Here's an article: http://www.nature.com/articles/srep21804 http://www.nature.com/articles/srep21804

itchyouch 9y ago

From what I recall, they are seen as normal proteins by the immune system, thus not targeted. A simple illustration on prions was to imagine it like a busted cable end that would break the socket it plugs into, then the socket would break other cable ends plugged into it. This would occur until all sockets and cable ends were broken in the same way.

phkahler 9y ago
Decades ago, we had a PCMCIA card that did exactly that. A bent pin distorted the plastic in the socket and that led to more bent pins. Of course you had to try to force them in to propagate the problem and we never tested to see how many generations it could last. Once discovered we threw out all defective hardware which was just a few cards by then.
- jacobush 9y ago
  I have heard this one before!
jandrese 9y ago
It's the Zip Drive click of death for your body.
- LordKano 9y ago
  I was going to make this same point.

abetusk 9y ago

Not a direct answer to your question (because I don't know) but there's a couple doing research into a cure for prion disease because one of them (Sonia Vallabh) has it. Eric Minikel has been blogging about their research [1] [2], maintains an active Twitter presence [3] and has GitHub [4] repositories on the issue. The blog has a lot of information for anyone wanting to know more about bioinformatics, basic research and prion disease in particular. [1] http://www.cureffi.org/ http://www.cureffi.org/ [2] http://www.cureffi.org/about/ http://www.cureffi.org/about/ [3] https://twitter.com/cureffi https://twitter.com/cureffi [4] https://github.com/ericminikel https://github.com/ericminikel

dmix 9y ago
> Sonia and I set out on a quest to re-train ourselves as scientists. We both started taking night classes, reading papers, calling up scientists, going to conferences. We left our old careers and found jobs in research labs, and eventually enrolled at Harvard Medical School, where we are now PhD students in biological and biomedical sciences. Wow, what a great story. Inspiring that you can change careers mid life and be successful. Thanks for sharing.

dllthomas 9y ago

> What would a cure for prion diseases even look like? Well, I mean, in some way the prion behaves differently than its normal counterpart. A molecule that interacted with that in such a way as to destroy the prion would seem to be a cure, right? At least, if not otherwise too harmful...

s0rce 9y ago
Or bind with it such that it is now inert, refolded back to a proper configuration or label it for destruction by the immune system.
amelius 9y ago
Or how about a molecule that binds to the harmful part of the prion?

dnautics 9y ago

If we do devlop a cure for prion diseases, short of a biofilter in a transporter beam, it will probably be some sort of directed antibody that magically only recognizes prion form of the prion protein, sequesters it and prevents spread; and maybe if we're clever at molecular engineering, also recruits the body's natural capability to clear these proteins (insulin-degrading enzyme).

scythe 9y ago

There are molecules that cause prions to "refold" back into the healthy form. The problem is that so far every such known molecule is highly toxic, e.g. guanidinium chloride.

dragonwriter 9y ago

> What would a cure for prion diseases even look like? You'd need something that responded to the physical conformation difference in the prion (which is clearly possible because prion disease is exactly a difference in behavior based on that) in a way which somehow selectively disrupts or expels the prion form of the protein (while different reaction is clearly possible, the desired difference is less clearly acheivable.) I suppose some kind of nanomachine that actually physically reconfigured proteins from the prion conformation to the healthy one might also be plausible, eventually.

ajnin 9y ago
The particularity of prions is that when they come into contact with the normal form of the protein, they can change its conformation to create a new prion (that's how the disease spreads). In that light I think an "anti-prion" protein should be possible, going around the body converting prions back into healthy molecules.

Cybiote 9y ago

We can look at kuru survivors who sadly, recently underwent rapid natural selection. Among this population are those possessing a variant of the prion protein gene that conveys strong resistance to prion diseases and the propogation of misfolded prion proteins. Here's an article: http://www.nature.com/articles/srep21804 http://www.nature.com/articles/srep21804