6). These results reinforce the association between methionine at codon 129 and the production of type

1 PrPres and valine at codon 129 and the production of type 2 PrPres. BSE is the only animal prion strain with demonstrated pathogenicity for humans. While it is tempting to suggest that scrapie might represent the animal reservoir that results in some cases of sCJD, there is no epidemiological evidence to support this hypothesis. The pathogenicity of new or newly described animal prion diseases for humans selleck chemical is unclear and this is particularly true for H- and L-type BSE, atypical scrapie and for chronic wasting disease (CWD), all of which are probably consumed. Human susceptibility has been modeled by attempted transmission to (humanized) transgenic mice with sometimes conflicting results, depending on the transgenic model used and depending upon whether central or peripheral tissues are examined.[102-106] We have attempted to establish whether PMCA can model the molecular component of these hypothetical cross-species transmission events.[107] The existing data correspond well with the established facts. First, PrPSc in vCJD brain samples amplifies

find more most efficiently in humanized mouse MM substrate, less efficiently in MV substrate and not at all in VV. Cattle BSE PrPres is less efficient than vCJD, but shows the same substrate genotypic preference. Sheep scrapie fails to amplify AMP deaminase detectably in any of the three substrates; however, sheep BSE PrPres does amplify, again with a codon 129 preference for methionine (Fig. 7). We are currently extending this approach to encompass atypical scrapie, H- and L-type

BSE and CWD using human rather than humanized PMCA substrates. In the same way that animal reservoirs cannot be completely excluded as causes of individual sCJD cases, neither can other environmental sources, such as medical procedures. The known routes of iatrogenic CJD acquisition are historically growth hormone therapy, dura mater grafting, corneal grafting and certain highly specialized neurosurgical procedures. The secondary transmission of vCJD by blood transfusion and experimental evidence showing the efficiency of the transfusion of viable blood cells between scrapie and BSE-infected and naive sheep have prompted a reappraisal of transfusion-transmitted CJD, including consideration being given to the possibility of prion blood testing or filtration.[25, 26, 108, 109] Blood transfusion is the original and most extensively used cellular therapy, but we may be on the threshold of a new era of cellular therapies based on embryonic stem cell and induced pluripotent stem cell technologies.