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PROOF, MRM Proteomics turn the peptides
VANCOUVER, British Columbia—A pair of prominent Vancouver-based organizations are partnering to develop revolutionary diagnostic blood tests to help clinicians manage organ failure patients more efficiently and effectively. The Centre of Excellence for the Prevention of Organ Failure (PROOF Centre) and MRM Proteomics recently announced a collaborative effort to identify protein signatures that can be used to indicate various disease states.
MRM Proteomics spun off from Genome BC Proteomics Centre at the University of Victoria to provide an interface to disperse and commercialize the basic research being done into an industrial setting. Today, MRM Proteomics is a contract research organization providing advanced protein quantification and proteomic services to the pharmaceutical, biotechnology and diagnostics industries. It possesses a large portfolio of peptides to bring to assays, and experience running the assays themselves.
The PROOF Centre brings to the partnership its clinical input as a not-for-profit organization dedicated to developing blood tests for chronic organ disease. Its non-targeted approach to searching for gene expressions or biomarkers to improve patient care complements MRM Proteomics mass-spectrometry approach. The PROOF Centre's strong computational team and approach and experience deciphering statistics and analyzing large-scale, complex data allow it to conduct the data mining, quality control of the data and processing the results of the assays using standard operating procedures.
"The two entities are the experts at doing what we do best—leading technology and assay development and generating high- quality data," says Dr. Andrew Munk, president and CEO of MRM Proteomics. "It makes sense for MRM Proteomics to be working together with the PROOF Center to get the maximum value out of that data."
Although the use of peptides and proteins as markers of disease states has a host of applications and could theoretically be used to monitor almost any illness, the PROOF Centre's focus lies primarily with chronic organ disease. In particular, its present focus is on patients with chronic heart failure, chronic lung disease and chronic kidney disease.
The organizations' joint project will attempt to develop and refine blood tests that use peptides and proteins to help monitor treatment of heart failure patients, determine a lung disease patient's stability and risk of repeated lung attacks and monitor a kidney disease patient's progress toward end-stage kidney failure.
Using peptides to quantify disease states such as these can be considerably more economical than the expensive and arduous process of developing antibodies for an ever-growing number of biomarkers. MRM's PeptiQuant assay technology allows for the quantification of hundreds of proteins at a time. This process' other advantages over antibody development include requiring significantly lower volumes of biological fluids—20 microliters versus hundreds of microliters, and much less time—a matter of a few months compared with six months to a year or more.
The commercial opportunities for bringing PeptiQuant MRM assays into the clinical lab are twofold. First, these assays are ideally suited for animal models because of the low cost and their effectiveness with a minimal volume of blood. Additionally, because some animals and humans have peptides in common, theoretically a common peptide in an animal could translate easily to a human model. Second, this style of assay could be used in conjunction with pharmaceutical companies early in the drug development pipeline to learn the proteins affected by and the efficacy of a drug perhaps as early as Phase I/II trials. These assays could be seen as a companion diagnostic, supplementing or reducing the need to look at panels of biomarkers at preclinical phases and develop a host of antibodies for them early in the drug discovery process.
All of MRM's assays have internal standards, which are critical to the robustness of the assays.
"There are many ways to run assays, but what's being done at the Proteomics Centre is really the right way to go," says Janet Wilson-McManus, chief operating officer of the PROOF Centre. "We're looking forward to working with them and getting into the clinic."
Sensitivity has historically been a stumbling block with mass-spectrometer assays, but the methods employed by MRM Proteomics produce a surprising level of precision.
"We've managed to get down to picograms per milliliter sensitivity in undepleted plasma," says Munk.
Farther down the pipeline, MRM is developing mass-spectrometry based assay platforms that are benchtop-sized, and the organization says multiplex assays for these platforms allow for a much higher throughput.