A woman who has died of vCJD, varient Creutzfeldt-Jakob disease aka mad cow disease, did not have the same type of the protein/prion that most victims have.
Her brain was examined by researchers at the Institute of Neurology, at University College London, who found it had an unusual pattern of disease and carried out a genetic analysis. This showed that her version of the prion protein was different from all other previous victims of the infection. In vCJD it is the patients' own prion protein that is subverted by the infection; it alters shape, forming clumps that fatally clog up the brain. About 40% of the population carry the so-called MM variant, found in all victims so far identified, but her VV type is shared by around 10% of the population.
I don't know what exactly is the difference between the VV and MM genotypes or how that changes the resulting structure of the prion protein. But if another genotype can contract vCJD from having eaten contaminated, there maybe a few more people that will suffer. It also means that whatever makes MM different from VV is not enough to stop a prion from changing the original protein to another prion.
There is a precedent for prion diseases affecting people with MM and VV prion-types differently. Kuru, a brain-wasting disease similar to BSE which struck a cannibalistic tribe in Papua New Guinea, had different incubation times according to people's genes. The word kuru means "trembling with fear".
Now that is interesting. It could be that people with different genotypes will suffer differently. A different time scale could be one way that it could manifest. A slightly different change in the brain tissue could be another part of that.
Its sad that people have to suffer because we turned herbivorous cattle into cannibals. At the same time it has spurred research into what otherwise may have languished in the annals of biochemistry as another strange way proteins act. Creutzfeldt-Jakob and scrapies are rather rare, as are other prion diseases such as Fatal Familial Insomnia, and while curious, they probably wouldn't have lead to the funding that this outbreak in the UK has lead to. Squeaky wheels getting oil and stories that bleed, lead.
4 comments:
Certainly if you run PAGE and Agarose gel electrophoresis you must realize that even in a well controlled situation results can vary and in this case you are dealing with a system with trillions of variables and of course it will be odd. I am sure that in some corner of the infinite universe there is an organism which has the destructive complement of this prion coded in it's genome and if someone were smart and could create a dna sequence for that protein and gene dope them, it would likely cure them :) Maybe folding at home could help? Just my random thought for the day.
A sort of anti-prion to catalyze a refolding back to the proper form? The biggest hurdle I see there is that we don't really know how the prion does it in the first place. So to get something to reverse it...
I think a slightly better approach, as long as we're spinning proteins, might be to make something to recognize the prion form and tag it with ubiquitin. Then let the cell take over from there.
I see we are in a contest for solving this problem (game on) so I will give my new best approach. Having just done monoclonal antibodies in the lab, has anyone tried ...
Well I googled so I didn't duplicate someone elses reasoning and voila!
http://www.nature.com/nature/journal/v422/n6927/abs/nature01457.html
quote from the article :)
"These findings indicate that immunotherapeutic strategies for human prion diseases are worth pursuing."
I searched for ubiquitin protein information for a paper and found your article. thanks for the help! also, I you may be interested in Science Magazine's current webinar: Science Magazine's Webinar: The Ubiquitin-Proteasome Pathway
Post a Comment