[genegenie (OP)]

I understand that prion diseases such as Creutzfeldt-Jakob disease can be inherited (due to a mutation in the PrP gene), or acquired by transmission. Does anyone know the proposed mechanism involved in infectious prion diseases ie. how does this variant protein (that contains no genetic material) alter the conformation of endogenous Prp proteins?

[NakedScientist]

The current theory is that the rogue prion induces a conformational change from an alpha-helical, globular structure to the fibrous beta-pleated architecture characteristic of PrPsc. How it does this is not known. It's a fascinating area...

TNS

[bezoar]

So the, why does it take so long for the symptoms of the disease to manifest?

Bezoar

[genegenie (OP)]

Apparently it takes a while for the variant proteins to accumulate and cause symptoms. It's amazing, and quite frightening!

[bezoar]

A while?  Twenty years or so?  It is amazing and frightening.  I was wondering if the body didn't mount some kind of defense and then finally succumb.  For something that takes that long, you'd think over a twenty year period, medical science could find some way to interrupt the process.

Bezoar

[chris]

Well, there are multiple ways to interrupt the process, including antibodies, but they are only any use if given before the person becomes symptomatic. Since the disease follows an accelerating course once neurological symptoms appear, initiating treatment at that stage is a bit like slamming the door once the horse has bolted.

The disease takes a along while to manifest because initially there are very few infections prion particles to initiate the conformational change. However, as more prion proteins are converted to the pathological form the abundance of abnormal prion grows exponentially since, in essence, it catalyses its own production.

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

[bezoar]

So then, is there an antibody to Mad Cow Disease, or I think you all call it BSE?  And if so, why not immunize everyone with any possible exposure?  Is there any test to detect it before it becomes symptomatic?

Bezoar

[genegenie (OP)]

I wasn't aware that there is treatment available....I'm keen to hear more about that. As far as I know, diagnosis can only be confirmed by autopsy. Build-up of these variant proteins cause plaques that  damage the brain.

[chris]

A novel feature of human BSE is the accumulation (presumably by amplification) of the abnormal prion in peripheral lymphoid tissue PRIOR to the onset of clinical neurological symptoms.

A man from the southwest of the country, by sheer serendipity, underwent appendicectomy a couple of years before being diagnosed with variant CJD (human BSE). Subsequent re-examination of the appendix specimen (which for some reason had been kept, I can't remember why) revealed the hallmark deposits of vCJD. This led to tonsilar biopsy being used in suspected cases.

The only way to diagnose the condition with certainty, during life, is by brain biopsy.

In terms of interventions, researchers have found that blocking certain parts of the immune system (with monoclonal antibodies) can stop prion transmission and amplification, but as I said before, only before it has become clinically manifest.

Chris

This had led to tonsillar biopsy

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

[bezoar]

And so, what's the rest of the story?  Did he receive monoclonal antibodies, and if so, was he cured or was the disease held in check?

Bezoar

[Ylide]

You'll be happy to know that a researcher at the National Institute of Health has come up with a way of treating prion-infected meats to eliminate the infectivity of said prions.  I stumbled across his work in the course of a paper I was writing on the horrible things that are happening to our food supply.  This made me feel a bit better...check it out.

http://www.nih.gov/news/pr/may2003/ninds-05.htm


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[chris]

In the above-mentioned (and linked) paper it says

"The scientists found that they were able to retain the basic texture and flavor of the processed meat while reducing the prions to non-infective levels. This may have application in improving the safety of meat products."

...so who tasted the (prion-contaminated)meat before and after treatment to conclude that the processed meat retained "the basic texture and flavor" ! [xx(]

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

[tweener]

From the sound of what they were testing on (hot dogs), I don't think there would be much flavor or texture worth retaining.

------------------------
No words of wisdom here.

[Ians Daddy]

Agreed.

[Ylide]

They probably fed it to cows.

In seriousness, they probably tasted the meat before adding the prions, then afterwards checked for prions before tasting it again.  

Besides, the proteins in processed meats are pretty much denatured already from the processing, so it's not like pressure and heat are going to make it any worse.



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[chris]

The point is that prions are clearly not denatured by the kind of processing that is used to prepare 'convenience foods', hence the 120+ cases of human BSE. Prions have been found to be resistant to autoclaving. Indeed contaminated surgical instruments, used previously on individuals who were later found to have been incubating CJD at the time of their brain surgery, have been implicated in the transmission of the disease to other patients.

Furthermore, not long ago a report found that in Germany brain-derived material was still finding its way into German sausages and indeed a friend of mine cut a thin section through such a sausage and stained it with a subtstance that highlights the presence of brain tissue. The test was positive. A paper also appeared in one of the medical journals based on the same test that predicted some types of sausage contained upwards of 15% brain tissue. Germany defended the use of this material by citing the low frequency of BSE in their country. But what they couldn't explain was the huge disparity between the number of cases of BSE you would expect to find in Germany - based upon the number of cows imported from the UK where the frequency of BSE was well established - and the number of cases of BSE that Germany actually reported. Perhaps we can cure BSE... just by shipping cows to Germany


"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

[Donnah]

Chris, so if Prions are resistant to autoclaving, how can surgical instruments be sterilized for protection?  Would submerging them in alcohol work?

[chris]

No. The only way to prevent infection is to throw away the kit.

This has led to the production of single use instruments for certain surgeries and in high risk individuals.

Chris

"I never forget a face, but in your case I'll make an exception"
 - Groucho Marx

[Ians Daddy]

Good God! Does nothing kill these prions? What about freezing or burning? Or nukes? Or bleach? If not, can these things be used in any way constructive, as in an antidote?

[bezoar]

So Chris, do you eat beef?

Bezoar