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Caprion Launches MRM-MS-based CNS Assay as Part of Push into Protein Discovery Panel Business

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NEW YORK (GenomeWeb) – Proteomics firm Caprion this week launched its CNS ProteoCarta panel for the study of central nervous system diseases.

A multiple-reaction monitoring mass spec-based assay that measures the levels of 142 proteins linked to neurological disorders including Alzheimer's and Parkinson's disease, the panel is the first of several such products aimed at specific disease areas that Caprion plans to launch in the coming year, the company said.

The panel emerged from a collaboration between Caprion and the Foundation for the National Institutes of Health's Biomarkers Consortium and Alzheimer's Disease Neuroimaging Initiative, Daniel Chelsky, the company's chief scientific officer, told ProteoMonitor.

The effort was similar to a previous collaboration between the Biomarkers Consortium, ADNI, and Rules-Based Medicine (now Myriad RBM), in which these parties used RBM's immunoassay-based platform to screen Alzheimer's patient samples for potential protein markers in CSF and plasma.

Having observed that project, Chelsky said, Caprion decided to propose a similar collaboration using its mass spec technology to measure proteins of interest in CNS disorders.

"We went to the Biomarkers Consortium and said, 'why don't we set up an assay that is specific to your interest,'" he said. The consortium provided a list of 240 proteins, 142 of which Caprion was able to develop sufficiently sensitive, reproducible MRM-MS assays for.

Using those assays, the company and its collaborators generated data on 310 samples from Alzheimer's patients, subjects with mild cognitive impairment, and controls. Caprion and the Biomarkers Consortium are currently working together on an analysis of these results that they hope to publish, Chelsky said.

While immunoassays like the RBM panel typically offer an advantage over MRM-MS in terms of sensitivity, Caprion's mass spec-based approach is more versatile, he said, as new MRM assays can often be developed more quickly and cheaply than immunoassays.

Myriad RBM's panels, "while they can be very good panels, are fairly fixed," he noted. "The big difference with the mass spec approach is that because we don't rely on antibodies, we're really not constrained by the time it takes to establish individual antibody assays."

Given this advantage, Caprion now aims to build out additional MRM panels in areas like oncology, offering them as a base product that individual clients can customize according to their specific needs.

What we've found is that when you come to [a client] and just say, 'give us a list of proteins and we can go after it,' that can work," Chelsky said. "But it actually gets people more motivated to know that an assay panel exists and that they simply have to modify it for their needs."

According to Chelsky, Caprion is currently in discussions about such an application of the CNS ProteoCarta panel with a non-profit that has requested to add to the panel 50 new proteins related to their disease of interest. The company has also run the panel in its original form for several drug companies as part of their Alzheimer's programs, he said.

Myriad RBM remains the leading name in the protein biomarker discovery panel space, but in recent years a number of other firms have moved into this space. Olink Biosciences, for instance, launched a discovery panel business in 2011 that it bolstered last year with a co-marketing deal with Fluidigm under which it offers its proximity elongation assays on that company's HD real-time PCR platform, allowing researchers to measure in a single run the levels of up to 92 proteins in as many as 96 samples. The company currently offers two discovery panels, one in oncology and one for cardiovascular disease, and is planning panels in inflammation and animal pharmacodynamics.

Somalogic has also moved into the discovery panel business with its SOMAscan platform, which uses its Slow Off-rate Modified Aptamer, or Somamer, affinity reagents to simultaneously quantify 1,129 protein analytes. Since launching the platform two years ago, Somalogic has run more than 40,000 samples as part of more than 140 studies. The company generated $10.5 million in revenues from the product in 2013 and expects to more than double these revenues this year.

Now-defunct NextGen Sciences also made a go at the panel business, trying, like Caprion, to develop collections of MRM-MS assays to specific disease and research areas. The company developed a series of protein marker panels, but was unable to generate much customer interest in the products and eventually went out of business in 2012.

While this would seem to bode poorly for Caprion's panel effort, mass spec has become a much easier sell in recent years, Chelsky said, noting that the company has collected a large amount of data demonstrating the sensitivity and reproducibility of its assays.

In fact, he said, before the company could get access to the ADNI samples used to develop the panel, it had to do significant work to demonstrate to the organization its assay's performance.

"In order to get [the samples] released, we had to convince [ADNI] that the assay was high quality, reproducible, sensitive," he said. "We were given replicate samples and blinded to those replicates. They wanted basically to make sure that we got the same data if we analyzed the same sample on one day or the next week or the next month. So it was a long process to demonstrate to them that this was an assay they could actually trust."

The CNS ProteoCarta panel, which the company runs on Agilent's 6490 triple quad as well as AB Sciex's 5500 and 6500 instruments, is able to quantify proteins at levels approaching a nanogram per mL and a median coefficient of variation of 20 percent. Chelsky noted that if researchers are interested in subsets of proteins identified as potential markers in screens using the overall panel, Caprion can create smaller assays using heavy labeled peptide standards that will bring down CVs significantly.

Another factor driving customer comfort with MRM-MS approaches, Chelsky said, is the launch last October of Integrated Diagnostics' MRM-MS-based Xpresys Lung test, for which Caprion did much of the early mass spec work.

"That has made a big difference in terms of getting people on board," he said. "We were [Indi's] mass spec lab for the first two and a half, three years. We built a very large MRM assay, to 377 proteins; we screened many samples for them; and we eventually transferred the assay to their CLIA lab."

"That was a big boon to the field, showing that you could use the mass spec to triage a large number of proteins and find something actually useful," he said.

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