Innovations and New Directions

Despite the majority of the information on CJD on this site being rather negative and hopeless, there are a number of places where future work can be done and where interesting things are happening with regard to prion diseases like CJD.

With a strong understanding of the state of current CJD research, one can easily identify the main areas needing more research. The number one area that future work needs to focus on is the molecular mechanism for the conversion of regular PRNP into disease-state PRNP. This is the missing piece in our understanding of the mechanisms of CJD progression. Infection is simple enough, it comes through eating or being exposed to prion-infected tissue. What we don’t know is how exactly the prion does its magic once it reaches endogenous PRNP. Kong et al. brought us one step closer to understanding the mechanism for conversion with their 2013 paper.  This needs to be taken further.

Second, understanding risk factors should be a priority as well. A lot of good genomic work is being done to find SNPs and loci other than PRNP’s which are associated with CJD and other prion diseases. If we can identify who is genetically at risk, we can keep an eye out for signs of the illness. Of course, without our first priority, the mechanism, we will not be able to create many effective treatments to help these at-risk individuals.

Third, Cai et al. touch on another interesting factor, which is the ability of PRNP to modify histones. Perhaps we should think about why a membrane protein should have some kind of epigenetic capabilities? Is this just an in vitro phenomenon?

Figure 1. DNA winding around histone proteins in chromatin packing. Each nucleosome contains histone proteins, which PRNP has been shown to modulate. This may exert some epigenetic control over the DNA region to which it binds. [Google Images]
Lastly, there are a lot of papers out which talk about varying levels of CJD. “Clinical” and “Subclinical” are often used but don’t always refer to the same stage of the disease. This is just starting to come out in the literature as CJD becomes more widely known. Many authors are attempting to clarify what is and is not CJD, and exactly how much phenotypic variance there is within the disease (Bishop et al., 2013; Head and Ironside, 2012). Up until now essentially any prion-related disease in humans was slid under the title of CJD, although there are some subtle differences in these variants of Creutzfeldt-Jakob. Additionally, the field needs to be more unified on whether variant CJD, heritable CJD, new variant CJD, and many of the other technical distinctions are actually separate disease states or just different aspects of the same disease either contracted in different ways or progressing differently. This is not so much a future research endeavor, but if the field is to accomplish what it wants to, it needs to set an agenda and start to unify its lexicon.

In terms of innovative and interesting future treatment ideas, these were covered a bit in the CJD treatment section, since there aren’t really any current treatments. To re-iterate, some of the new strategies being considered:

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Figure 2.Table of potential treatment strategies for CJD. [M.Edward Quach]
 While CJD does affect only a small number of people each year, the diagnosis is currently a death sentence, and a swiftly executed one at that. However, good science is being done to further our understanding of prions and prion diseases. Future research on the points highlighted above, and work on the therapies being developed currently can change that.