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Myriad, Cambridge Researchers Collaborating on Protein Tests for Depression, Schizophrenia

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Despite initial setbacks, Myriad Genetics is moving ahead with development of protein biomarker panels for a variety of psychiatric disorders.

In collaboration with Sabine Bahn, head of the Cambridge Centre for Neuropsychiatric Research, the company is exploring proteomic tests for purposes including diagnosis of schizophrenia, identification of individuals likely to progress to schizophrenia, and prediction of patient response to anti-depressant medication.

Myriad entered the psychiatric protein biomarker space with its 2011 purchase of Rules-Based Medicine, of which Bahn's firm at the time, Psynova Neurotech, was a subsidiary. RBM and Psynova, where Bahn was a co-founder and director, had developed a 51-protein diagnostic for schizophrenia called VeriPsych, which they launched in 2010.

Upon its acquisition of RBM, Myriad highlighted the company's mental health portfolio, and VeriPsych specifically, as areas of focus going forward. Myriad CEO Peter Meldrum noted that the US military had "shown a strong interest" in using the test.

Shortly after the RBM acquisition, however, Myriad discontinued sales of VeriPsych.

"While the data indicated that proteomic signals correlating with schizophrenia existed, the control populations used for validation [of the test] were not the most optimal for clinicians seeing these patients, and the test was not as useful to them as was hoped," Richard Wenstrup, Myriad's chief medical officer, told ProteoMonitor this week.

While VeriPsych was effective at distinguishing between healthy and schizophrenic individuals, clinicians were more interested in having a test to distinguish schizophrenia from other psychiatric conditions, Bahn said. "And we had not at the time [of the test's launch] assessed the differential diagnostic capabilities of the test."

The large number of proteins comprising the test also proved a drawback, Bahn told ProteoMonitor, as this made it rather expensive, at $2,700.

During its time on the market, VeriPsych was ordered by more than 30 clinical centers, and these centers were "reasonably happy" with its performance, she said, but the high price and lack of differential diagnostic ability limited its appeal. She suggested that the test had been launched prematurely for "company strategic reasons."

Since pulling the test from the market, Myriad has continued to work with Bahn on proteomic tests for psychiatric disorders, though the company said it was too early to discuss a timeline for bringing any of these tests to market.

According to Bahn, Myriad identified through market research three main areas of interest among psychiatrists: predicting patient response to anti-depressants; identifying at-risk individuals who will progress to schizophrenia; and identifying patients with symptoms of depression who will develop bipolar disorder.

With regard to identifying patients who will progress to schizophrenia, Bahn noted that this is a significant clinical need as only 20 to 30 percent of people who present with mild symptoms of psychosis will ultimately develop schizophrenia.

"So this is a big issue, obviously, because you are treating 70 percent of people who will not get the disease," she said. "You not only stigmatize them, but you also put them on drugs that can have some serious side effects."

Bahn said that she and her team have had some success identifying protein markers predictive of conversion to schizophrenia. Likewise, she said, they have identified "some good markers that predict response to certain types of antidepressant medication before people are put on the drugs."

Studying samples from a six-year longitudinal study of roughly 3,000 patients with disaffective disorder, the researchers have also managed to identify markers that appear helpful in predicting which patients will go on to develop bipolar disorder, Bahn said.

They are also continuing their work on a differential diagnostic for schizophrenia, with the goal of paring down the 51-protein VeriPsych panel to a set of 10 to 20 proteins.

Bahn and Myriad are also exploring alternative sampling methods that could bring the price of the test down, she said. "We would like, if we can, to avoid shipping the samples on dry ice, because that is actually more costly than running [a large number of markers]."

Bahn said that she was particularly interested in dried blood spots as a potential sampling method. Dried blood spots have recently emerged as an area of significant interest in clinical proteomics, with biomarker and diagnostics firms like SISCAPA Assay Technologies, Healthtell, and SpotOn Clinical Diagnostics exploring the method's potential to offer improved convenience and cost savings compared to conventional blood samples.

Bahn is also exploring targeted mass spec as a clinical platform for the assays she and her team are developing. She has developed a multiple-reaction monitoring mass spec assay capable of multiplexing between 60 and 70 proteins. Currently, she said, the assay provides high-quality data on around 50 of these analytes.

MRM-MS is attractive from a cost perspective, Bahn noted, as adding additional analytes to an assay is relatively inexpensive compared to the cost of additional antibodies required for immunoassay-based panels.

Myriad is also interested in the MRM-MS approach, she said. Wenstrup declined to provide any specifics beyond noting that the company "has familiarity with several different technology platforms capable of analyzing blood proteins, including mass spectrometry."

"Myriad," he said," is currently evaluating these platforms for accuracy, reproducibility, scalability, and ease of sample collection and transport."

While Myriad has made significant inroads into proteomics with its purchases of RBM and, last week, of Crescendo Bioscience, both of these firms' products rely primarily on immunoassays.

Bahn and her team are also performing discovery work using mass spectrometry, and, indeed, she noted, the original discovery work for the VeriPsych panel was done primarily using mass spectrometry.

She uses mainly Waters instrumentation in this work, she said, adding that she makes significant use of the company's MSE data independent acquisition technology. Her lab does its targeted work on a Waters' triple quad, as well, though Bahn noted that the researchers are currently looking to upgrade this instrument and are evaluating new machines from three different vendors.

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