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Nuclea Mass Spec Plans Take Shape with Upcoming Launches of RUO, Clinical Assays

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NEW YORK(GenomeWeb) – Nuclea Biotechnologies this month will launch a set of mass spectrometry assays covering roughly 55 protein biomarkers as part of its recent move into mass spec-based proteomics.

The company plans to follow that launch with the release toward the end of the year of a multiplex mass spec assay for insulin, proinsulin, and c-peptide, which it will offer as a clinical test out of the new CLIA facility it is building in Cambridge, Massachusetts.

The multiplex assay provides something of a template for the company's clinical mass spec ambitions going forward, said Nuclea COO Mary Lopez, noting that it will focus largely on applying mass spectrometry to relatively established protein markers for which existing immunoassay-based tests have poor performance.

In this the company's clinical mass spec model is less like that of firms like Integrated Diagnostics or Applied Proteomics, which have worked to develop and launch mass spec panels composed of novel protein markers, and more akin that of large clinical reference laboratories like Quest Diagnostics, which, for instance, has developed mass spec tests for angiotensin, insulin-like growth factor 1, and thyroglobulin in an effort to improve on previously existing immunoassays for these analytes.

"For the mass spec-based tests that we will be offering, we will try to choose analytes that benefit from being run on a mass spectrometer," Lopez told GenomeWeb.

"Not every test needs to be run on a mass spec — some tests you can do just as well with an ELISA," she noted. But, she added, in a number of cases, antibody tests suffer from a lack of specificity that mass spec can provide. This is particularly the case for tests where proteins are present in multiple forms, some of which are more clinically relevant than others.

"A mass spec really shines when you need to be able to measure different forms of the protein and so you need that selectivity the mass spec can give you," Lopez said, citing the insulin, proinsulin, and c-peptide as an example.

Mass spec can also overcome issues with antibody interference that can hamper test reliability. In the case of existing immunoassays for insulin, interference can cause results between tests to vary by as much as ten-fold, Lopez said, adding that while insulin tests could prove useful for monitoring conditions like diabetes and metabolic syndrome, many physicians decline to use them due to their poor reliability.

The insulin test stems from a previous collaboration between Nuclea and Thermo Fisher Scientific. Lopez was previously head of Thermo Fisher's Biomarker Research Initiatives in Mass Spectrometry (BRIMS) Center before joining Nuclea, with five other BRIMS employees, to lead the company's move into mass spec protein work.

In 2014, a team led by Lopez published a study in Proteomics detailing a method for quantification of intact insulin and its therapeutic analogs using Thermo Fisher's mass spectrometric immunoassay (MSIA) technology combined with the company's Q Exactive instrument. The Nuclea test, Lopez said, uses a very similar protocol, likewise combining MSIA and the Q Exactive. 

From the perspective of clinical mass spectrometry, use of the high-resolution Q Exactive instrument is interesting in that most clinical proteomics mass spec work has focused on developing multiple-reaction monitoring workflows for use on triple quadrupole machines. Lopez said, however, that she believed other testing companies had begun to incorporate the Q Exactive into their labs.

"I don't believe we're the first," she said, though she added that Nuclea would be the first lab she was aware of to use MSIA and the Q Exactive to enable multiplex quantitation of the three markers.

Owned by Thermo Fisher, MSIA is a pipette immunoenrichment system that uses microcolumns activated with antibodies to isolate target proteins for mass spec analysis. Similar to other immunoenrichment approaches, the method enhances mass spec sensitivity and throughput by reducing sample complexity.

As opposed to immunoenrichment approaches like SISCAPA that enrich samples at the peptide level, post-digestion, MSIA enriches at the protein level, prior to digestion. This makes it well-suited to applications like the Nuclea insulin test where the aim is to measure multiple forms or fragments of the same analyte.

Nuclea will offer the insulin, proinsulin, and c-peptide test both as a multiplex measuring all three molecules and as separate tests that can be ordered individually, Lopez said. She noted that the tests will be billable under existing CPT codes for these analytes, meaning that "they will be revenue generating from the start."

The company is also planning additional mass spec tests for other analytes where existing immunoassays perform poorly, Lopez said, giving as an example parathyroid hormone.

"Primarily our focus will be to commercialize tests that are already needed and that we know mass spec can do better [than existing methods]," she said.

Nuclea is likewise sticking to established markers for the 55-protein RUO panel it plans to launch at the end of this month, Lopez noted.

"Most of the markers we will be offering in the biomarker RUO [panel] will be markers that are in the public domain and that are clinically important in the areas of oncology, diabetes, metabolic syndrome, and other chronic diseases," she said.

These panels will consist of traditional multiple-reaction monitoring assays on a triple quadrupole instrument.

While the MRM panel offering is new for Nuclea, CEO Patrick Muraca two years ago purchased the assets of a similar business from defunct proteomics firm NextGen Sciences. Lopez noted that those assets included intellectual property to a number of protein biomarkers and mass spec assays and added that in the future the company plans to add more unique tests to the panel based on intellectual property held by Nuclea.

Nuclea is also pursuing some discovery work. Specifically, it announced last month that it has partnered with Aelan Cell Technologies to develop and commercialize new biomarker tests and companion diagnostics aimed at cancer, metabolic disorders, neurodegeneration, and age-related conditions. 

Nuclea will do mass spec-based protein analysis of the stem cells used by Aelan in its test development, while Aelan will perform genomic analyses. Nuclea will have the opportunity to commercialize markers discovered and validated through the collaboration, Lopez noted.

"Many of the chronic diseases we are interested here at Nuclea are age-related," she said. "So we are very interested in markers that are important in the aging process and that may be related to, for instance, whether [disease] treatments will be successful in one patient versus another."

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