PROOF, MRM Proteomics turn the peptides

Protein signatures could become companion diagnostics to optimize drug discovery and patient care management

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VANCOUVER, British Columbia—A pair of prominentVancouver-based organizations are partnering to develop revolutionarydiagnostic blood tests to help clinicians manage organ failure patients moreefficiently and effectively. The Centre of Excellence for the Prevention ofOrgan Failure (PROOF Centre) and MRM Proteomics recently announced acollaborative effort to identify protein signatures that can be used toindicate various disease states.
MRM Proteomics spun off from Genome BC Proteomics Centre atthe University of Victoria to provide an interface to disperse andcommercialize the basic research being done into an industrial setting. Today,MRM Proteomics is a contract research organization providing advanced proteinquantification and proteomic services to the pharmaceutical, biotechnology anddiagnostics industries. It possesses a large portfolio of peptides to bring toassays, and experience running the assays themselves.
The PROOF Centre brings to the partnership its clinicalinput as a not-for-profit organization dedicated to developing blood tests forchronic organ disease. Its non-targeted approach to searching for geneexpressions or biomarkers to improve patient care complements MRM Proteomicsmass-spectrometry approach. The PROOF Centre's strong computational team andapproach and experience deciphering statistics and analyzing large-scale,complex data allow it to conduct the data mining, quality control of the dataand processing the results of the assays using standard operating procedures.
"The two entities are the experts at doing what we dobest—leading technology and assay development and generating high-qualitydata," says Dr. Andrew Munk, president and CEO of MRM Proteomics. "It makessense for MRM Proteomics to be working together with the PROOF Center to getthe maximum value out of that data."
Although the use of peptides and proteins as markers ofdisease states has a host of applications and could theoretically be used tomonitor almost any illness, the PROOF Centre's focus lies primarily with chronicorgan disease. In particular, its present focus is on patients with chronicheart failure, chronic lung disease and chronic kidney disease.The organizations' joint project will attempt to develop andrefine blood tests that use peptides and proteins to help monitor treatment ofheart failure patients, determine a lung disease patient's stability and riskof repeated lung attacks and monitor a kidney disease patient's progress towardend-stage kidney failure.
Using peptides to quantify disease states such as these canbe considerably more economical than the expensive and arduous process ofdeveloping antibodies for an ever-growing number of biomarkers. MRM'sPeptiQuant assay technology allows for the quantification of hundreds ofproteins at a time. This process' other advantages over antibody developmentinclude requiring significantly lower volumes of biological fluids—20microliters versus hundreds of microliters, and much less time—a matter of afew months compared with six months to a year or more.
The commercial opportunities for bringing PeptiQuant MRMassays into the clinical lab are twofold. First, these assays are ideallysuited for animal models because of the low cost and their effectiveness with aminimal volume of blood. Additionally, because some animals and humans havepeptides in common, theoretically a common peptide in an animal could translateeasily to a human model. Second, this style of assay could be used inconjunction with pharmaceutical companies early in the drug developmentpipeline to learn the proteins affected by and the efficacy of a drug perhapsas early as Phase I/II trials. These assays could be seen as a companiondiagnostic, supplementing or reducing the need to look at panels of biomarkersat preclinical phases and develop a host of antibodies for them early in thedrug discovery process.
All of MRM's assays have internal standards, which arecritical to the robustness of the assays.
"There are many ways to run assays, but what's being done atthe Proteomics Centre is really the right way to go," says JanetWilson-McManus, chief operating officer of the PROOF Centre. "We're lookingforward to working with them and getting into the clinic."
Sensitivity has historically been a stumbling block withmass-spectrometer assays, but the methods employed by MRM Proteomics produce asurprising level of precision.
"We've managed to get down to picograms per millilitersensitivity in undepleted plasma," says Munk.
Farther down the pipeline, MRM is developing mass-spectrometrybased assay platforms that are benchtop-sized, and the organization saysmultiplex assays for these platforms allow for a much higher throughput.

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