? MDS for Detecting Heterogeneous Protein Multimers
The present inventors have developed a prototype method for differentially detecting a multimeric form from a monomeric form of a multimer-forming polypeptide, called “Multimer Detection System (MDS)”. Fundamental features of MDS is the ability to detect various conformations of protein multimers with high sensitivity.
? Example of MDS Application: Abnormal Prion Detection in Blood
MDS showed high sensitivity and specificity when applied to detect multimeric abnormal prion proteins (PrPSc). In the clarification, normal form of the prion protein (PrP) is PrPc (cellular or normal form of prion) and the infectious form of prion protein is PrPSc (scrapie or infectious form of prion). MDS could detect preclinical scrapies using blood samples. MDS is currently being optimized to detect amyloid-beta oligomers in human blood samples.
The core technology of PeopleBio is a platform method to differentiate and detect various multimeric forms of a multimer-forming polypeptide from its counter monomers using MDS system. The multimer-forming polypeptides are considered as crucial pathological factors in various diseases or disorders; however no method has been developed to differentially detect the multimeric forms from the monomeric form of multimeric-forming polypeptides.
Background and unmet needs: Generally, the multimerization of polypeptides constitute misfolded proteins, which deviated from its normal function. However, the multimeric forms often cause diseases or disorders. In particular, a protein exists as a monomer in normal conditions which can be converted to a multimer (or aggregated form) in abnormal conditions (e.g., by the conversion to a misfolding form). For example, the diseases or disorders are caused by abnormal aggregation from misfolding of proteins including Aβ peptide and tau protein implicated in Alzheimer’s disease, prion implicated in Spongiform encephalopathy, α-synuclein relating to Parkinson’s disease, and so forth.
Discovery and Achievements: Various methods were tried to detect abnormal proteins but the problem was the heterogeneous multimeric forms of abnormal proteins. Hence, specific antibodies couldn't detect all multimeric conformations of abnormal proteins. MDS was designed to detect heterogeneous multimeric proteins in body fluid. In body fluid, especially, blood is complex sample with high concentrations of many proteins. PeopleBio accumulated the know-how and has much experiences in optimizations and detections of target proteins. MDS was developed to detect target proteins at very low concentration. Three-dimensional reaction, sample volume optimization, and concentration-inducing reagents were used to increase the sensitivity of the detection. To increase the specificity, the company developed unique buffer conditions to lower the possibility of false positivity. MDS detected the prion multimers in plasma at early pre-symptomatic as well as clinical stages.