The future of biomarker assays

Ralph McDade explains why more is better when it comes to data used to identify meaningful biomaker patterns.

What is DiscoveryMAP?
Ralph McDade. DiscoveryMAP v 1.0 is Rules-Based Medicine’s (RBM) newest and most comprehensive biomarker assay, measuring 189 clinically relevant proteins from a single 500 microlitre sample of serum or plasma. The service offers drug developers broad coverage of the most physiologically relevant pathways, providing key biological information, leads for further study and support for go/no-go decisions. The sheer number of important analytes in a single test increases the odds of identifying new protein biomarker patterns in almost any drug development or diagnostic discovery project.

What prompted the development of the service?
RM. When it comes to identifying meaningful biomarker patterns, more data is better. DiscoveryMAP was designed in response to requests from our biopharma customers who recognised the value of combining our various human MAP services into a single comprehensive assay.

How does RBM’s DiscoveryMAP service compare to alternatives?
RM. First, DiscoveryMAP utilises RBM’s proprietary multi-analyte profiling (MAP) platform to quantify key blood-based biomarkers representing dozens of important biological pathways. With this platform, customers receive the most robust, quantitative data compared to any other available proteomic service or platform technology. All samples are processed in RBM’s CLIA-certified lab using proprietary reagents and software to give the most accurate and reproducible protein measurements.

Second, multiplexing allows all of these assays to be processed from a 500 microlitre sample of serum or plasma, compared with single-plex platforms, such as ELISA, which would require 10 to 15 millilitres of sample. And finally, all samples are processed on an industrialised, automated platform that enables the discovery of biomarker patterns made up of multiple proteins, many with small, yet reproducibly detected, changes.

Once a customer receives his or her initial data, is that the end?
RM. No, and that’s another reason DiscoveryMAP is so unique. While being a cost-effective way to measure 189 analytes, it’s also the first step of a process that can yield a new custom panel tailored for each customer’s needs. DiscoveryMAP includes biomarkers known to be important in the major disease indications for drug development. Once a pattern is discovered, we can convert those biomarkers into a new custom panel for high-throughput sample processing in clinical trials as a service from RBM or supplied to the customer as an optimised kit. And since all of our work is done on a clinically validated platform, our biomarker pattern discoveries are more easily applied throughout remaining clinical trials.

Are there any noteworthy success stories to date?
RM. In fact, DiscoveryMAP has already been successfully used in the discovery of new diagnostic biomarker panels. RBM’s partnerships with Psynova Neurotech, Satoris, Inc., and leading academic researchers have yielded diagnostic biomarker patterns that have been validated with multi-site sample collections for applications such as neuropsychiatry, neurodegenerative disease, nephrology, immunology and cardiology. RBM is also partnering with several pharmaceutical companies to develop companion diagnostic products. Looking forward, RBM is seeking additional collaborations to develop diagnostic and companion diagnostic applications based on patterns detected with DiscoveryMAP.

You mentioned the ‘RBM approach’ earlier. Can you tell us more about that?
RM. Let’s use an example to illustrate the RBM approach. Thirty years ago, researchers found that blood cholesterol was a good marker for cardiovascular risk. Unfortunately, elevated cholesterol only identified roughly 50 percent of the at-risk population. Eventually, research uncovered the role of lipoproteins (HDL and LDL), which showed better predictive value than cholesterol alone. Today, research has identified 25-30 blood-based markers that provide even better predictive value in assessing cardiovascular risk.

The problem is that measuring all of these markers has been prohibitively expensive and unreliable. Applying multiplexing technology, the RBM approach provides drug developers and researchers with a cost-effective and reproducible way to measure dozens of relevant clinical markers and pinpoint the biomarker patterns that are either directly involved in the disease process or are useful surrogate markers. When those patterns can be reliably measured, the efficiency of drug development is accelerated while achieving greater efficacy and safety.

Ralph McDade is Strategic Development Officer for Rules-Based Medicine and has held this post since the company’s inception in 2002. He was formerly Chief Scientific Officer for Luminex Corporation from 1996-2002, where he was closely involved with the development of xMAP technology. He received his PhD in Microbiology from the University of Texas Southwestern Medical School in 1980.