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New Markers Enter Uncharted Diagnostic Territory
Emerging Biomarker Assays Are Poised to Change the Course of Disease Management. Here's How.
A patient is receiving a routine physical exam. As he sits in the doctor's office, he thinks about the fact that heart disease runs in his family. He feels healthy, but is he at risk? As part of a comprehensive check-up, the physician decides to run some tests.
One of the tests is new; it measures a biomarker that can help predict a person's risk of future cardiac trouble—even if they appear to be in perfect health. Based on the results, the physician can create a treatment plan specifically for the patient.
Clearly, the patient benefits from this new biomarker assay—but so does the physician, since she will have more information about the patient's health, and will be able to deliver the best treatment for the situation. The entire healthcare system benefits, as well, because proactive disease management is typically less expensive than major surgeries and hospital stays.
"New biomarkers can change the course of disease management," says Kathleen Orland, director, Immunoassay Strategic Marketing for Beckman Coulter. "If you are able to identify and measure the right biomarker, you can gain far more information about a disease and whether or not someone is at risk—even if they have little to no symptoms."
The benefits are compelling, which is why Beckman Coulter has been collaborating with researchers, physicians and customers to pursue revolutionary new assays for promising biomarkers. Exciting developments are under way in three key areas: cardiac disease, prostate disease and high-risk pregnancy.
Two Promising Markers for Cardiac Disease
Despite dramatic medical advances over the past 50 years, cardiac disease remains a leading cause of death globally and the number one cause of death in the United
States1. Cardiac disease accounts for 30 percent of deaths worldwide, according to the World Health Organization (WHO). In the United States, almost 700,000 people die from cardiac disease each year, and researchers are eager to identify new biomarkers to assess risk.
"Treatment and management can help address the heart disease problem, but another effective strategy for curbing this chronic illness is prevention," says
Marie-Jeanne Yerna, Ph.D., scientific marketing manager for Beckman Coulter. "Healthcare providers want to get better at predicting someone's risk, so they can properly monitor and treat them before major symptoms arise."
This input comes in part from a Beckman Coulter Cardiac Scientific Advisory Board, a group of key cardiologists, researchers and emergency physicians who give feedback and guidance on new assays and practices.
One of the most popular biomarkers remains cardiac troponin I, which helps determine if a patient has had an acute myocardial infarction (AMI) or other damage to the heart.
Since its introduction, the sensitivity and efficacy of the troponin I assay has increased substantially, and today the Beckman Coulter Access AccuTnI assay is one of the most popular tests in this area. Laboratories use it to determine even very low troponin I levels. The assay detects both the intact cTnI molecule and degraded forms of the molecule, which can help detect AMI in late-presenting patients.
Building on this success, the company is working on a prototype research assay that aims to increase sensitivity even more. The high-sensitivity cTnI (hs-cTnI) research assay* has been shown to detect even lower concentrations of cTnI, allowing physicians to identify subtle patterns of change in myocardial health.
"For the first time, we are able to measure cTnI levels in almost all healthy subjects," says Yerna. "This will help physicians define what is 'normal' when it comes to plasma levels of cardiac troponin I. With this insight, and a better sense of what early risk patterns look like, we can improve the diagnoses and treatment of patients with cardiac disease, and potentially prevent heart attacks from occurring."
Beyond Troponin I
Another emerging marker in the cardiac area is PAPP-A. Historically, it's been used to assist in the assessment of fetal well-being. But in 2001 a landmark paper in the New England Journal of Medicine reported that PAPP-A could also be a marker for unstable plaques within arteries2.
It was an exciting discovery in the world of cardiac disease. Beckman Coulter began working with cardiologists and researchers to develop a research-use-only (RUO) assay* called cPAPP-A which is commercially available in a microplate format. "It has analytical sensitivity of 0.18 IU/mL," says Yerna, "so it allows researchers to precisely measure the lowest PAPP-A levels found in non-pregnant, healthy population."
A large trial is currently under way to confirm the results of preliminary studies by Beckman Coulter. Upon the trial's completion, work will begin on an automated assay for routine clinical diagnostic testing.
Better Detection of Prostate Disease
Worldwide, roughly 395,000 men are diagnosed with prostate cancer each year, and the prostate specific antigen (PSA) assay helps physicians make this determination.
The guidelines on the high-end and low-end are clear: If a patient's PSA level is 10 ng/mL (nanograms per milliliter) or higher, a biopsy is usually performed; and if it is under 2 or 2.5 ng/mL, no immediate follow-up steps are usually taken3.
Issues arise, however, between 2 and 10 ng/mL. Results in this range are considered "increased risk," but out of this group, only 25 to 35 percent of the patients will ultimately be diagnosed with prostate cancer. The rest will have a non-cancer prostatic condition, yet they will have endured the anxiety, expense and discomfort of a prostate biopsy4.
"If the PSA level falls between 2 and 10 ng/mL, many physicians struggle with the decision of whether or not to proceed with a biopsy," says Bernard Cook, Ph.D., scientific marketing manager for Beckman Coulter. "It's hard to know what to do with these PSA results."
To help guide their decision-making, doctors look at the ratio of free PSA to total PSA, and perform a digital rectal examination (DRE). But soon they will have another diagnostic tool: the Hybritech
p2PSA** assay.
The Access Hybritech p2PSA measures the [-2]proPSA molecule, an isoform of free PSA. Studies have demonstrated that when p2PSA measurements are combined with
Access Hybritech PSA and free PSA measurements, the resulting index demonstrates a significant improvement in clinical specificity for prostate cancer detection, relative to PSA and % fPSA alone, in the PSA range 2-10 ng/mL.
As a result, p2PSA will provide physicians and patients with additional critical information to guide follow-up and treatment decisions for men with elevated PSA levels.
The p2PSA assay is commercially available in Europe and plans are under way for United States Food and Drug Administration (FDA) submission as well.
"We collaborated with key prostate cancer researchers to develop the p2PSA assay" says Cook. "Our goal is to help physicians make the right diagnosis, and reduce the instances of unnecessary biopsies. This helps lower healthcare costs, and creates a
better outcome for patients."
Early Identification of High-Risk Pregnancy
Preeclampsia, one of the most serious complications of pregnancy, is another
area where new biomarkers are needed. A major cause of maternal and neonatal morbidity and mortality, preeclampsia is a condition found only in human pregnancies.
The good news: biomarkers for preeclampsia have been identified and are under development. These new assays should allow doctors to establish an early and definitive diagnosis, thereby managing and treating patients more effectively. The tests may help direct healthcare costs to those women needing the increased medical surveillance.
The biomarkers were identified by a team of scientists from Harvard Medical School. In a landmark paper published by the New England Journal of Medicine in 2004, they reported that preeclampsia involves an imbalance of two proteins: placental growth factor (PIGF), which promotes blood vessel development; and sVEGF-R1, which restricts blood vessel development.
Based on this research, Beckman Coulter is partnering with researchers and physicians to develop these biomarkers as automated diagnostic tests for routine use on the Access systems***. Working with collaborators from two hospitals and using Beckman Coulter prototype assays, a recently completed study showed that women with preeclampsia have lower levels of PIGF and higher levels of sVEGF-R1 than women with normal pregnancies, clearly separating them from normal pregnancies. This paper will soon be published in the American Journal of Obstetrics & Gynecology.
"Some women with rapidly advancing preeclampsia report few or no symptoms," says Linda Rogers, Ph.D., scientific marketing manager for Beckman Coulter. "This puts them and their baby at a serious health risk. But with better diagnostic tools, doctors will be able to identify preeclampsia earlier and provide the necessary treatment and monitoring to lead to a safe delivery for both mother and baby."
Turning a Corner
Current methods for managing prostate disease, cardiac disease and high-risk pregnancy have recognized limitations, and more can be done to advance understanding and treatment on all fronts. New biomarkers—and their accompanying diagnostic assays†—have the potential to change the course of disease management.
"It's exciting to collaborate with researchers and healthcare providers to develop these new tests and learn the best way to apply them," says Orland. "We are filling unmet needs—and at the same time delivering solutions that will aide physicians, lower healthcare costs, and, most important, improve patient outcomes."
*For Research Use Only. Not for use in diagnostic procedures
**In development for US market, pending FDA approval
*** Assays are in development, not available for IVD use
†Not intended as off-label promotion of any Beckman Coulter diagnostic product
References
1 Gebel, Erika, Heart Disease a Leading Cause of Death Worldwide, U.S. Department of State, www.america.gov, July 24, 2008
2 Bayes-Genis, Antoni; Conover, Cheryl A.; Overgaard, Michael T., et al., (2001)
Pregnancy-Associated Plasma Protein A as a Marker of Acute Coronary Syndromes, New England Journal of Medicine, Volume 345:1022-1029, Number 14
3 Kawachi MH, et al. (2007) National Comprehensive Cancer Network (NCCN)
Clinical Practice Guidelines in Oncology, V.2.2007
4 Prostate Specific Antigen (PSA) Test Fact Sheet, National Cancer Institute, U.S. National Institutes of Health, www.cancer.org
Beckman Coulter, the stylized logo, Access and Hybritech are registered trademarks of Beckman Coulter, Inc. AccuTnI is a trademark of Beckman Coulter, Inc.
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