Search

Prion diseases are invariably fatal infectious diseases of the central nervous system. The prion protein has been identified as the underlying causative agent as PrP knockout mice (prnp0/0) are resistant to infection. This suggests that a significant reduction in the expression levels of PrPc should interrupt disease progression. Accomplishing this in vivo, upon presentation of symptoms, requires a mechanism that significantly reduces prnp mRNA levels while lacking potential side effects that may be cytotoxic or lethal to the host. Hybrid hammerhead ribozymes (HyHamRzs) include both a helicase recruitment signal and a tRNAVal promoter. HyHamRzs offer a means of highly specific and significant mRNA cleavage. In this study, data demonstrate increased activity granted to HamRzs by the addition of the helicase recruitment signal. Results show that three different HyHamRzs, targeting different locations along the full length prnp mRNA, reduced expression levels by greater than 95% relative to the control. It is postulated that HyHamRzs, modified to enhance serum stability and delivered intravenously to neurons by forming a complex with the modified rabies virus G protein (RVG), may offer a potential gene therapy strategy. [ABSTRACT FROM AUTHOR]

Background: The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob Disease (vCJD) have led to profound changes in the production and trade of agricultural goods. The rapid tests currently approved for BSE monitoring in slaughtered cattle are all based on the detection of the disease related isoform of the prion protein, PrPd, in brain tissue and consequently are only suitable for post-mortem diagnosis. Objectives: In instances such as assessing the health of breeding stock for export purposes where post-mortem testing is not an option, there is a demand for an ante-mortem test based on a matrix or body fluid that would permit easy access and repeated sampling. Urine and urine based analyses would meet these requirements. Results: Two dimensional differential gel eletrophoresis (2D-DIGE) and mass spectrometry analyses were used to identify proteins exhibiting differential abundance in the urine of BSE infected cattle and age matched controls over the course of the disease. Multivariate analyses of protein expression data identified a single protein able to discriminate, with 100% accuracy, control from infected samples. In addition, a subset of proteins were able to predict with 85% ± 13.2 accuracy the time post infection that the samples were collected. Conclusion: These results suggest that in principle it is possible to identify biomarkers in urine useful in the diagnosis, prognosis and monitoring of disease progression of transmissible spongiform encephalopathy diseases (TSEs). [ABSTRACT FROM AUTHOR]