Early cancer detection is the big prize for biomarker developers, but markers for other diseases may come to fruition sooner.
Cancer is really hard because there are so few cancer markers of any credence out there,” says Steven A. Carr of the Broad Institute. But other diseases don’t have the same problem. For example, cardiovascular disease has a substantial set of known markers, such as creatine kinase, fatty acid-binding proteins, and
Carr’s team is collaborating with clinicians to identify biomarkers of myocardial infarction—also known as a heart attack. A therapeutic procedure known as alcohol septal ablation induces a controlled heart attack and allows the researchers to use each patient as his or her own control by taking blood samples before and after the procedure.
Commenting on the work, David F. Ransohoff of the University of North Carolina, Chapel Hill, says, “This kind of design should be great for strong discovery because so many potentially confounding explanatory variables can be eliminated by using the patient as their own control.”
Carr and coworkers were able to identify more than 100 proteins expressed differentially in myocardial infarction patients (Nat. Biotechnol., DOI: 10.1038/nbt.1899). Carr points out that such candidates, although meriting a closer look, are still a long way from being proven as bona fide markers.
Efforts toward markers of various neurological diseases are also moving forward. For example, the Michael J. Fox Foundation for Parkinson’s Research is coordinating a study to validate markers of disease progression in Parkinson’s disease. The Parkinson’s Progression Markers Initiative (PPMI) is taking promising candidate biomarkers and moving them to the next level of verification, leading to possible validation. The driving force behind PPMI is the desire to provide an infrastructure for testing of potential markers, says Mark Frasier, director of research programs at the Fox Foundation.
The five-year initiative is currently recruiting 400 patients with newly diagnosed Parkinson’s disease and 200 age-matched controls. A comprehensive set of biological samples—blood, urine, cerebrospinal fluid—and clinical data will be collected from every patient through the same protocols at all test sites, Frasier says. “If you’re going to build the infrastructure, you want to be sure that the data you’re collecting is going to be useful,” he adds. The common protocols will allow data to be compared across patient cohorts.
“It takes multiple cohorts and multiple discoveries to verify particularmarkers,” Frasier says. “That’s been the roadblock to moving markers through the pipeline. We’re hoping PPMI will greatly accelerate that movement.”
In another neurological disorder, Alzheimer’s disease, a panel of protein biomarkers is heading toward validation studies. Alzheimer’s is a disease for which a definitive diagnosis can be obtained only after death.
Proteome Sciences, a company based in the U.K. and Germany, is working with Simon Lovestone at the Institute of Psychiatry at King’s College London, to develop the nine-protein panel. The proteins were selected from 40 that were discovered by comparing biobank plasma samples from patients whose Alzheimer’s was later confirmed during autopsy with those of patients without Alzheimer’s. The study, which includes 1,000 samples, started in May and is slated to run through the end of the year, according to Ian Pike, chief operating officer at Proteome Sciences. If the verification study pans out, the company plans to market the biomarker assay for research use, he says, pending further studies for possible diagnostic use.
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