Words like “schizophrenia” and “bipolar disorder” have guided psychiatric treatment for decades, but they may be meaningless labels that mask a lack of real knowledge about the molecular events behind these related constellations of symptoms. That’s the critical view that greeted the latest edition of the psychiatrists’ “bible,” the Diagnostic and Statistical Manual of Mental Disorders, or DSM-5, published by the American Psychiatric Association in late May.
Among those critics is Thomas Insel, director of the National Institute of Mental Health, who highlighted the debate about the DSM-5 in an April blog post. Insel called for the discovery of biomarkers that could both re-categorize common mental illnesses and open doors to better therapies. This work has already begun at companies such as Austin, TX-based Myriad RBM, a subsidiary of diagnostic testing company Myriad Genetics (Nasdaq:MYGN) of Salt Lake City, UT.
Myriad RBM, formed in 2002 as Rules-Based Medicine, was an early developer of protein assay panels that test not only for known disease biomarkers, but also for other proteins that might be unsuspected troublemakers. As a partner with researchers at the University of Cambridge, UK, RBM developed an experimental test for schizophrenia in 2009. That led to an ongoing collaboration with Roche—one of a number of notable partners RBM gained before it was acquired in 2011 by Myriad.
Myriad, a genetic testing pioneer founded in 1991, built its business around its early flagship test, BRACAnalysis, which looks for variations in two genes that significantly elevate a woman’s risk of breast cancer. Myriad controlled the market for BRACA gene testing due to its portfolio of gene patents, but some of those have now been invalidated by the US Supreme Court in its June 13 ruling. The market impact of the ruling on BRACAnalysis is yet to be seen, but competition is likely to increase among providers of tests based on single genes that powerfully increase disease risk. However, many diseases result from an interplay of multiple gene mutations, and diagnostic companies are using their knowledge of those interactions to add value to their diagnostic products.
Myriad moved in that direction when it acquired RBM for $80 million, augmenting its DNA and RNA screening repertoire with proficiency in protein detection.
“Few other companies have expertise in all three,” says Craig Benson, president of Myriad RBM. “We sort of used to say we complete the Triple Crown of molecular biology diagnostics.” The company’s protein assay panels now cover a range of focus areas including oncology, cardiovascular disease, and inflammation.
Myriad RBM’s primary customers are pharmaceutical companies and research institutions that are looking for help in drug development and clues to the core mechanisms of disease. Benson, who joined Rules-Based Medicine at its birth as a spin-off from Austin, TX-based Luminex (NASDAQ: LMNX) says the company had to persuade clients at first that they should look beyond the biomarkers that were already known to be associated with the diseases they were researching and use RBM’s fuller “multiplexed” assay panels.
RBM’s founding principle was that complex diseases such as neuropsychiatric disorders would only be fully understood by examining multiple molecular factors, and the relationships among those factors in different individuals.
“We almost forced customers to think about things in a different way,” Benson says. “It was a little bit of evangelizing in the early days.”
Since then, the company has tested preclinical and clinical trial samples from more than 400 companies. “They continue to come back after finding biomarkers for unintended or intended consequences,” Benson says.
Working together, Myriad and Myriad RBM are helping investigators with studies that may identify the molecular mechanisms behind disease, and reveal differences between patients with the same outward symptoms. Using this data, drug developers seek to identify the patients most likely to benefit from therapies targeted at specific disease mechanisms. They can also try to eliminate those least likely to benefit in clinical trials of an experimental drug.
The ultimate goal of this molecular-level diagnosis is called personalized medicine or “precision medicine”—the use of treatments tailored to each individual’s disease state, not to a catchall diagnosis.
NIMH director Insel is advocating this type of approach for the physically based mental disorders known by terms such as schizophrenia, bipolar disorder, and major depressive disorder. Guided by the DSM, psychiatrists now diagnose these brain disorders by observing behaviors such as disordered thinking, loss of emotion, and hallucinations. But patients with these varied diagnoses can have similar symptoms, and their diseases may share some of the same root causes in genetic variations.
As Insel said in his April post, NIMH now plans to support research that zeroes in on specific symptoms and their related biomarkers, no matter what traditional diagnosis patients have received. But he acknowledged that biomarker-based diagnosis is still only a goal in psychiatry, because robust tests have yet to be commercialized.
Myriad RBM is working on it, along with other disease diagnostics. Benson says most illnesses can be traced to the DNA code of an individual as well as the pattern of proteins produced by that individual under the influence of the environment and other factors that affect gene expression. He says Myriad RBM’s protein screens and Myriad’s gene-based tests can help pharmaceutical companies to learn more about how their drug is metabolized in the body, predict significant side effects, find new uses for old drugs, and possibly get a failed drug back on track by identifying the right patient population for it.
Myriad RBM customers can pick cafeteria-style from a selection of standard protein tests that are useful for general discovery, or choose specialized panels for research in specific diseases. Clients can also order customized combinations of several multiplex panels to evaluate their samples. The tests are run at RBM’s lab in north Austin, which employs 100 workers. The Myriad subsidiary also has product development and manufacturing units at Saranac Lake, NY, and Reutlingen, Germany.
Myriad RBM contributed $23.6 million to Myriad’s $496 million in revenues for the year ended June 30, 2012. The RBM acquisition also gave Myriad access to new sets of patient samples as it develops its pipeline of molecular diagnostic tests, the parent company said in its 2012 annual report.
The Texas subsidiary is moving toward commercialization of its own clinical diagnostic products, including companion diagnostics for new therapies in development by its pharmaceutical company clients.
Among the tests in the works are biomarker assays to show molecular-level differences between schizophrenia and bipolar disorder. Another experimental test makes distinctions between bipolar disorder and major depressive disorder.
“That’s right in the throes of development,” Benson says.