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Prion Poison Prevention

Pills Power-Pry Proteins por Perfectly Proofed People
  [vote for,

As it happens, there is a group of diseases that have many names (scrapie in sheep, Mad Cow Disease in cattle, etc.), but a couple common features. They all gradually disable and eventually kill by causing a unique deterioration of brain tissue, creating hordes of tiny holes, such that the overall appearance becomes sponge-like. They all are caused by a rogue protein, which has the generic label of "prion". This protein is a natural thing that comes in two forms. One form is needed by the body; the other -- same protein, different SHAPE -- is devastating. It can somehow catalyze the needed form to switch to the bad form. That means there is more of the bad form present to cause still more catalysis of the needed form...until death occurs. Do note that this is not any sort of ordinary disease; it is more like a slowly accumulating poison.

Worse, prion proteins are tough. They can be ingested orally, survive the digestive process, enter the bloodstream, cross the blood-brain barrier, and go to work doing their devastation. More, they can also cross BACK through the brain-blood barrier, exit the body along with urine and feces, and contaminate plants that might be eaten, years later!, by other animals. I've just finished reading an article in a very recent SCIENTIFIC AMERICAN, and am now convinced that prions pose as much a long-term and insidious threat to humanity as any other disease in history. Prions can survive cooking, and even autoclaving! We are GOING to have to deal with them, so we might as well get started brainstorming -- before we don't have the brainpower any more to raise so much as a squall!

Here is my suggestion. The weakness of prions is that they ARE proteins, and all proteins are assembled by various biological processes. This means that other biological processes can disassemble them. The key tools that biology uses, to build/demolish proteins, are specialized compounds known as "enzymes". Often they are proteins, too. All enzymes are catalysts, enabling various bio-reactions to take place much faster than would happen if the enzymes were not present. I submit that we need to direct our research at enzymes suited to breaking down prion proteins. The cool thing about this is that enzymes are REALLY specialized. Bio-reactions are molecular-SHAPE-dependent! This means that an enzyme that can demolish the bad prion protein can entirely ignore the needed variant of that protein.

Once we have found some suitable enzymes, we genetically engineer bacteria to mass produce them, and simply add them to the diet, in pill form. This is perfectly analogous to something that some people do already. Those people are naturally unable to properly digest milk. They can take pills containg lactase, the enzyme that their bodies don't happen to produce, which properly breaks down milk during digestion. So, with respect to anti-prion pills, any prions that happen to become part of the diet can be destroyed before they reach the brain. Possibly those enzymes can also circulate in the blood and eliminate prions in the brain, too. Certainly we shouldn't hesitate to add those enzymes to all animal feed, lawn fertilizer, weed killer, etctera. EVENTUALLY, the world will be cleansed of this scourge, but first we have to find those enzymes.

Let's get started!

Vernon, Jun 02 2003

Some News https://science.sla...00-percent-accuracy
Humans poisoned by prions can now be absolutely, positively identified. [Vernon, Dec 23 2016]


       sp. protein. still reading.
po, Jun 02 2003

       I was right with you until the words "genetically engineer" appeared. Suddenly, my mind filled with images of fishbones. All in all, though, a rather abbreviated concept from [Vernon].
Cedar Park, Jun 02 2003

       UnaBubba, yes, but this is exacly why I'm discussing enzymes and not some other means of breaking down prion proteins. Enzymes CAN be that specific. Note that while the physical composition of a protein can often be portrayed as a longish chain of molecular sub-units, the overall protein is naturally found in a folded-up shape. Much computing power is now being devoted to attempts to predict exactly how a particular protein composition will fold up. Prions are odd in that they have two different mostly-stable shapes. Since almost all biological reactions are shape-dependent, we merely need to find an enzyme that operates only on the unique features of the bad prion shape.
Vernon, Jun 02 2003

       I'd be surprised if this isn't a line of research already being pursued somewhere. But then, I have been surprised before.   

       Oh, and [Cedar Park] - this actually looks like one of the rare occasions where GE isn't simply used as a magic wand.
-alx, Jun 02 2003

       What lurch said.   

       It is possible that these misfolded proteins occur naturally, every once in a while, so destroying them completely might not actually eliminate the problem. CJD occurs when there are significant numbers of misfolded proteins present so a screening process combined with a refolding/misfold elimination treatment should stop this turning into an epedemic. Unfortunately that's where my knowledge ends. What actual research is being done in screening and treatment is beyond my ken.
st3f, Jun 02 2003

       Lets just ban all that dirty, unhygenic, Mad-Cow-infected foreign beef and demand that they slaughter every last head of cattle, devastating their livestock industry so we can dominate them.   

       Oh heck, we're talking about US Beef aren't we?   

       BUY FRENCH!
FloridaManatee, Jun 02 2003

       It may not be simple to find such an enzyme. Those proteinaceous bad boys are extremely durable. C Gadjusek buried infected hamster brains in a garden for 2 years then dug them up and the prions were fine.
bungston, Jun 02 2003

       As a variation on the suggested idea, we might note that simply because a prion CAN somehow affect the needed protein, the prion must therefore possess something known as an "active site" --maybe more than one. So, we could look for appropriate molecules that can fit into and permanently lock up those active sites. With respect to ordinary diseases, such molecules are known as "antibodies".
Vernon, Jun 02 2003

       Rods: no floor. One of the abnormal isoforms is enough. It will just take longer. Vernon: your comment just now gave me a great idea. Not an enzyme for prevention of prion diseases but an actual treatment for infected animals / people. Prions function like a crystal in a saturated solution: they are like nucleating agents, catalyzing the transformation from the normal configuration to the bad one. What is needed is not an antibody (which does not get into the CSF very well) but a suicide substrate. This would be a molecule which was similar to normal prion protein, but when the bad prion stuck to the suicide substrate it would be irrevocably bound. Even if the prion remained in the animal, it would be stuck to the SS, biologically inert, and no longer able to catalyze anything. Prions and prion proteins are immunologically invisible, and so a suicide substrate likely would be as well - making it a tolerable drug (in this resepct, anyway). It would also be an excellent vaccine, mopping up any consumed prion proteins before they cause trouble.   

       The nice thing about drug development for prion diseases: no shortage of animal models.
bungston, Jun 02 2003

       [bungston] That is a great idea, but how is it different from what [vernon] described in his anno above?   

       It is a fascinating idea, whoever gets the credit. And it would seem to be relatively feasible too. We could call it suicidevernonbungstrate.
dijontoothpaste, Jun 02 2003

       Vernon's originally proposed enzyme would destroy the prions by breaking them down - a difficult feat. My SS would contain them: they would not be broken down, but would be neutralized, unable to cause trouble. This is exactly what Vernon proposed in his anno, but suggested that it be done with an antibody - thus Vernon did most of the mental heavy lifting. Instead of an antibody, why not just use a modified form of the natural substrate to accomplish this end: my meager addition. But I do like the "Bungstrate" term. As long as I hear nothing about "Bungstitutes".
bungston, Jun 02 2003

       bungston, I do know that antibodies also exist to signal the immune system to come-hither and clean up the invaders they have attached themselves to. SOME antibodies, however, may actually partially deactivate the disease, by attachment such as I described in my last annotation, while performing their signalling task. It was the deactivation-type of attachment that I was suggesting, without actually giving it a name. I was merely analogizing with "antibodies" as the closest equivalent. If "suicide substrate" is the correct description for the action I tried to describe, fine.
Vernon, Jun 02 2003

       You propose a different thing - which is fine. Antibodies which inactivate by binding to an active site do not necessarily mimic the substrate which is supposed to fit into that active site - in fact this in probably rarely the case. More likely the big bulky antibody just latches on nearby and by sheer bulk and steric hindrance prevents the site from doing its job. A suicide substrate looks and acts like the molecule which is supposed to fit into an active site - but it never comes back out.
The antibody approach has some advantages - 1: you can make an antibody to just about anything 2: in addition to just gumming up the works you call into play the immune system to clean things up. There are obstacles to making a prion antibody. One is that these antibodies are really hard to make, since the prion protein is widely conserved and everything has anergy to the normal isoform. Another is that antibodies might cross react with the normal form, which is constitutively expressed. A third is that Abs dont get into the CSF very well. The problem with the SS approach is that it invokes chemical engineering magic - maybe it is not possible to make a prion-protein like molecule which binds and does not let go.

       We have deviated from the enzyme idea, which is the best approach to making feed additives safe. If the enzyme breaks down more than it is supposed to, fine. Maybe dirt bugs could be cultured in dishes where most of the available carbon was in the form of prions, then select for those which survived best.
bungston, Jun 02 2003

       UB's link speaks more to the therapeutic stuff, not the feed additive enzyme.
bungston, Jun 03 2003

       jutta, I made this suggestion because so far all I've seen are worries about and explanations of the prion problem, but no offered means of dealing with it. For all I know, others have been working on exacly what I suggested, for some time. Perhaps it is obvious in hindsight, but first the sight of the idea has to be behind us, heh heh.   

       Certainly the discussion here has shown that the suggestion is not an easy one: if prion proteins are so stable, then finding a catalytic enzyme to break them down cannot be simple (bungston may have offered the best approach, offering bacteria ONLY a diet of prions to digest...). Anyway, it is still worth it, in my opinion, to suggest that the search be made! And ditto for the suicide substrate variant/alternate notion.
Vernon, Jun 03 2003

       Prion tainted land seems to stay that way forever. The bacteria you propose could be used in a bioremediation effort. If a gene for that specific enzyme (if such an enzyme could be found or designed) were added to a soil bacteria, this might represent a solution.
talldave, Sep 03 2003

       Good summary, now to the halfbakery...Like my Lung Washing (which I now think might be applied to inhaled anthrax) I was pointed to the Lung Brush. Here, the solution might also be the Brain Brush. Straighten out those curly, folded and twisted bothersome prions with the New Brain Brush! A short daily combing (especially after heavy meat consumption) keeps them straight, silky and manageable!
kamenmann, Sep 03 2003

       On one hand this is like saying "let's just wipe out every disease by creating antibiotics".   

       On the other hand I like alliteration.
Voice, Dec 23 2016

       On the third hand the incubation period for all the prion-beef eating British from 1990 to go mad cow has probably elapsed. And no mass madness I have heard of. At least not the disorganized stumbling around prion type madness.
bungston, Dec 23 2016

       Well, there was Brexit.   

       " I submit that we need to direct our research "   

       Ah, I love the smell of let's-all in the morning ...
normzone, Dec 23 2016

       I am imagining a time where electromagnetic frequencies are so specific we will be able to choose to break the molecular bond between two desired chains of atoms. Just irradiate the specific prion.   

       Of course there will always be side effects.
wjt, Dec 23 2016


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