Development of a Fit-For-Purpose LC-MRM-MS Assay to Measure Prion Protein in Cerebrospinal Fluid
Eric Kuhn, Eric Vallabh Minikel, Alexandra R. Cocco, Sonia M. Vallabh, Christina R. Hartigan, Stuart L. Schreiber and Steven A. Carr Broad Institute of MIT and Harvard, Cambridge, MA
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Eric Kuhn (Presenter) Broad Institute
Presenter Bio: Eric Kuhn is a Research Scientist at the Broad Institute in the Proteomics platform. An expert in peptide quantitation assays using stable isotope labeled standards and LC-MRM-MS, I have designed antibody and aptamer based enrichment (or depletion) strategies to increase the sensitivity and precision of protein measurements in complex biofluids (e.g plasma) to improve detection limits for potential biomarkers of ovarian cancer, breast cancer and cardiovascular disease. I have co-authored guidance documents that describe peptide standard specifications and targeted peptide measurement best practices. I have a BS in Biochemistry from the University of New Hampshire and have studied proteins and enzymes at Dupont, AutoImmune, and Millennium Pharmaceuticals.
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
Prion disease is a fatal and untreatable neurodegenerative disease caused by misfolding of the prion protein (PrP). PrP is a well-validated drug target for prion disease and candidate therapies are being developed to lower PrP levels in the brain. Using a 9-plex MRM assay, we were able to detect and quantify human PrP using either a heavy labeled protein standard or heavy labeled peptide standards using nanoelectospray LC-MRM-MS. CV for six peptides from heavy labeled protein was 9 – 23% across a concentration range of 2.4 – 240 ng/mL and results correlated to a commercial ELISA (rho 0.40 – 0.69). Further development will include transfer of methods to a clinical laboratory and validation in a regulated environment to support future clinical trials.
= Discovery stage. (17.55%, 2019 US)
= Translation stage. (42.72%, 2019 US)
= Clinically available. (39.74%, 2019 US)
