Scrapie is one of the transmissible spongiform encephalopathies (TSE). Transmissible, because the infection can be transmitted from one creature to another; spongiform, because the brain tissue of an infected animal looks like a sponge, when viewed with a microscope; encephalopathy, because it causes disease of the brain.
There is a family of TSEs. All are caused by prions; all are invariably fatal. Although they may have a long incubation time, they progress rapidly to death once symptoms become apparent. Thus, any clue about a possible treatment is encouraging to see...
There are many prion diseases; some primarily affect humans, while others affect animals. But humans who eat infected animals can get infected themselves. That is why mad cow disease (Bovine Spongiform Encephalopathy) is so worrisome.
Human Prion Diseases
- Creutzfeldt-Jakob Disease (CJD)
- Variant Creutzfeldt-Jakob Disease (vCJD)
- Gerstmann-Straussler-Scheinker Syndrome
- Fatal Familial Insomnia
- Kuru
Animal Prion Diseases
- Bovine Spongiform Encephalopathy (BSE)
- Chronic Wasting Disease (CWD)
- Scrapie
- Transmissible mink encephalopathy
- Feline spongiform encephalopathy
- Ungulate spongiform encephalopathy
The PNAS article, Hot spots in prion protein for pathogenic conversion, is not open-access.
However, a nice summary is openly available. The link appears to not be a permalink, so I am going to just copy the whole thing here. You still need subscription or institutional access to read the actual article.
Incidentally, I find myself linking to closed-access articles less and less, but this one had a cool picture...
Blocking prion formation
The conversion of a prion protein from its native form to its pathogenic form is poorly understood and difficult to stop. Kazuo Kuwata et al. identified a molecule that can interrupt the conversion of the scrapie protein to its infective conformation. The authors used a computer screening program to identify candidate molecules that could stabilize the native form by filling a pocket in the protein that deforms as it moves from its native state to a temporary higher energy form. From a list of 320,000 potential compounds, their program reduced the list to 624. Further refinement reduced the list to 59, 44 of which were tested in mouse neuronal cell cultures. One, called GN8, safely blocked the transformation of the scrapie protein in a dose-dependent manner. Live mice infected with the scrapie protein survived longer when given GN8. The authors also found that GN8 rescues the prion protein from its pathogenic deformation by intercalating its hot spots. A molecule like GN8 could be used to treat prion diseases, and computer-based screens may identify more suitable compounds. The authors say that their proposed strategy, termed "dynamics based drug design," may be applicable to other protein misfolding diseases. — P.D.
There are many obstacles to overcome before anything potentially therapeutic for humans is developed.
Comments
Many thanks for this.
I rarely miss new Papers about TSE's/Prion but missed this one. I have requested a copy of this Paper from the Authors.
Whilst I personally was not at a CJD Conference last week in Washington, a Presentation by a highly regarded Japanese Researcher most probably touched upon this and/or other compounds that the Japanese are currently looking at. It would be nice to know what *GN8* actually is ;-)
Since the majority of Japanese cases of CJD are linked to contaminated Dura Mater grafts, they specifically have this in mind in potential treatment research terms/drug delivery routes etc.
The greatest amount of progress that has been made thus far in treatment terms in CJD patients that I am aware of is with regards to Pentosan Polysulphate (or PPS). Original lab research going back to 1987 using Scrapie mouse models pointed us in this direction.
After a High Court Ruling in London in December 2002, we started treating CJD patients a couple of months later. Several Papers have been published in this regards. Work itself in patients is ongoing in real time and I am in regular contact with some of these families.
Court Injunctions were set in place (to varying degrees) which largely explains why little information has entered the public domain.
We do of course keep a look out for other potential treatment leads and are not complacent.
We think that it is unlikely that treatment wise, *one glove fits all* strains of human TSE's.
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I am glad that you mention "Incidentally, I find myself linking to closed-access articles less and less"
I am currently involved in a number of projects in several countries to encourage Authors to consider publishing in OA Journals or to self-archive TA Journal Papers into Institutional Repositories.
As such, I am very encouraged at your comment !!
Graham Steel
Information Resource Manager
CJD International Support Alliance
Posted by: Graham Steel | July 16, 2007 9:47 AM