The misfolding of proteins and their subsequent aggregation in the brain is thought to be the cause of a group of related neurological diseases including Parkinson’s, Alzheimer’s and the transmissible spongiform encephalopathies such as BSE, scrapie, vCJD and CWD (the ‘protein conformational disorders’, or ‘protein aggregation diseases’). The development of highly sensitive and specific diagnostic assays for these diseases is a high priority.

The majority of assay kits for BSE and scrapie in brain tissue seek to differentiate normal prion protein (PrPsen) from the abnormal, aggregated form (PrPres) with a proteinase K digestion step. As an alternative approach Microsens has been developing ligands (the ‘Seprion’ range) with specificity for PrPres. A group of polymeric compounds have been evaluated that have the ability to bind PrPres, under selective conditions, in BSE, scrapie, CWD and vCJD-infected bovine brain tissue. Recent observations have shown that Seprion ligands can bind a PrPsc-like material (the scrapie form of PrPres) in infected sheep blood (unpublished results).

An immunometric assay format has been developed, with the Seprion ligands immobilised directly to the wells of a microplate. After addition of bovine brain homogenate and direct capture of PrPres the bound prion protein is detected with a specific prion protein-specific antibody/peroxidase conjugate. This assay procedure is greatly simplified compared to the proteinase K digestion methods and is suitable for automation on an ELISA processor.

Assay kits incorporating the Seprion ligands are now available from Idexx Laboratories Inc, USA for the detection of PrPres in brain tissue from BSE and scrapie-infected cattle and sheep and in brain and lymphoid tissue from CWD-infected deer.

The Seprion ligands have also been coated onto magnetic microparticles and studies are underway on the capture of the abnormal prion protein from larger quantities of brain homogenate and blood fractions.

Microsens has also demonstrated that the Seprion ligand technology is applicable to the detection of the aggregated proteins present in Alzheimer’s disease (amyloid and tau proteins) and Parkinson’s (synuclein protein) (unpublished results).