Quantcast

Industry news that matters to you.  Learn more

Archives for May 2013

The Search for an Early Biomarker to Fight Atherosclerosis

Recently, the Journal of the American Heart Association published conclusive results from a study directed by Dr. Éric Thorin of the Montreal Heart Institute (MHI), which suggests for the first time that a blood protein contributes to the early development of atherosclerosis.

Dr. Thorin, his team and his collaborators discovered that the blood levels of angiopoietin-like protein 2 (angptl2) are six times higher in subjects with coronary heart disease than in healthy subjects of the same age. Their basic research study also revealed that angptl2, which is undetectable in young mice, increases with age in healthy subjects and increases prematurely in subjects who have high cholesterol and pre-atherosclerotic lesions. Entitled “Angiopoietin-like 2 promotes atherogenesis in mice,” this study was conducted using an animal model consisting of three to twelve-month-old mice.

These results represent a major advance in the prevention and treatment of atherosclerosis. “Although much work remains to be done to broaden our knowledge of this protein’s mechanisms of action, angiopoietin-like protein 2 may represent an early biomarker not only to prevent vascular damage but also to predict atherosclerotic disease,” explained Dr. Thorin.

For 15 years, Dr. Thorin, a researcher at the MHI Research Centre and full professor at Université de Montréal, has been interested in the evolution of artery function during the aging process and in the underlying mechanisms of atherosclerosis. More specifically over the past five years, he has looked at the role of this particular protein. Thanks to his work, we now know that angptl2 causes a high degree of vascular inflammation. Blood levels of this protein increase in patients with cardiovascular disease as well as in people with complications related to diabetes, obesity and cancer in which the small blood vessels are damaged, as all of these diseases are associated with chronic inflammation.

According to Dr. Anil Nigam, a cardiologist and specialist in cardiovascular disease prevention at the MHI and co-author of the study, “Prevention is the ideal solution to delay the onset of atherosclerosis, and an early blood marker such as angptl2—if future clinical studies confirm this finding—will serve as an important tool to identify at-risk subjects who do not present with any symptoms of atherosclerotic disease.”

Study: Angiopoietin‐Like 2 Promotes Atherogenesis in Mice

Source: Montreal Heart Institute

TGen and Riddell Announce Partnership for Biomarker Study of Concussive Injuries

Head protection plays a vital role in the health and safety of any athlete participating in helmeted sports. In a move that could help revolutionize football player safety, the Translational Genomics Research Institute (TGen), and Easton-Bell Sports through its Riddell brand, announced recently it would work together on a study designed to advance athlete concussion detection and treatment. Information gathered through the study will also be used to develop new football headgear and further refine updates to player monitoring technology.

“TGen welcomes this remarkable opportunity to join Riddell in a major research study with the goal of helping to objectively monitor a player on the field (with microelectronics combined with nucleic acid sequencing),” said Dr. Jeffrey Trent, TGen President and Research Director. “TGen’s work over the past several years in the area of head trauma is accelerating new insights to the critical study of concussion injury.”

The genesis of this potentially groundbreaking study is to merge a player’s genetic information with real-time microelectronic information captured by Riddell’s Sideline Response System (SRS). A highly sophisticated, data-intensive system, Riddell SRS provides researchers, athletic staff and players with a wide range of valuable information on the number and severity of head impacts a player receives during games and practices. Employed since 2003 by several well-respected research institutions, Riddell SRS has captured 1.8 million impacts from youth to elite football competition, and its data has led to impactful changes to rules, how the game is played and coached, and has informed new helmet designs.

“As the industry leader in football head protection, Riddell has the unique opportunity to advance TGen’s groundbreaking medical research into the brain as we work together towards identifying a way to accurately and quickly diagnose concussions in football players,” said Dan Arment, President of Riddell. “With Riddell’s commitment to player protection and history of innovation, we are hopeful that our collaboration with TGen will help us better protect athletes and lead us to meaningful advancements in helmet technology that move the game of football forward.”

A key question the study seeks to answer is: are the effects of sub-concussive hits identifiable through blood-based molecular information? “Based on our current information, we believe this study will have the unique ability to provide a molecular ‘risk’ and ‘recovery’ score, enabling physicians to better identify when a player might be expected to recover from the effects of the concussion and get back on the field,” said Dr. Kendall Van Keuren-Jensen, TGen Assistant Professor, whose technique for studying molecular information at a micro level will drive the research.

While the joint study will begin with football, the Riddell-TGen partnership has the potential to improve sports equipment manufactured by brands in the broader Easton-Bell Sports portfolio, including headgear for hockey, baseball, cycling, snowsports, and powersports. “As the awareness of head injury grows across all sports, supporting science like this will help us offer a more protective helmet solution to the athlete,” said Arment.

Local Institutes and Advocate to Join Study

As part of the study, TGen will work with the Barrow Neurological Institute whose B.R.A.I.N.S. (Barrow Resource for Acquired Injury to the Nervous System) program treats patients who have sustained a traumatic brain or spinal cord injury.

“Combining our neurological expertise and the information from our B.R.A.I.N.S. program, with TGen’s genomic knowledge and Riddell’s helmet technology, will provide great insight into how we measure concussions and how they affect the human brain,” said Dr. Javier Cárdenas, a neurologist and brain injury expert with Barrow Neurological Institute. “The genomic data could aid in the treatment process and will greatly add to the growing body of knowledge we’re acquiring about head injury patients.”

Joining Barrow will be athletic trainers from A.T. Still University and SAFE Football, which teaches alternative game-play techniques that reduce the number of head impacts while increasing competitiveness.

“Our partnerships with Barrow Neurological Institute, A.T. Still University, and Safe Football provide a multifaceted approach to identifying athletes in need of medical attention, to educating athletes on concussion and brain injury, to reducing the risk of injury through development of better techniques, and to improving treatment outcomes,” said Dr. Matt Huentelman, TGen Associate Professor and a co-investigator on the study.

Source: Translational Genomics Research Institute (TGen)

Cancer Biomarker Study Data Presented at the 2013 AACR Meeting

As we’ve done in previous years here at Biomarker Commons (AACR 2011 and AACR 2012), here’s a roundup of eight research studies on cancer biomarkers that were presented last month at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC. The theme of this year’s meeting was “Personalizing Cancer Care Through Discovery Science.”

  • Biomarker Analysis Identified Women Most Likely to Benefit From T-DM1

    According to data from a subanalysis of a phase III clinical trial that led the U.S. Food and Drug Administration to approve trastuzumab emtansine (T-DM1) in February, the amount of HER2 in tumors of women with metastatic, HER2-positive breast cancer might determine how much they benefit from the drug. The findings were presented by José Baselga, M.D., Ph.D., physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York.

    Source: AACR

  • Novel Serum Biomarker Bilirubin Predicted Lung Cancer Risk in Smokers

    Researchers from MD Anderson Cancer Center in Houston, Texas, used a unique multiphase study design for the metabolomics profiling of serum samples from non-small lung cancer patients, and showed that bilirubin is a potential biomarker for lung cancer risk prediction. Men who were smokers and had low bilirubin levels had increased risk for cancer incidence and mortality.

    Source: AACR

  • Biomarkers Discovered That May Help Predict Response to Drugs Targeting KRAS-mutated NSCLC

    Massachusetts General Hospital scientists have identified biomarkers that may help predict whether patients with KRAS-mutated non-small cell lung cancer (NSCLC) will respond to concurrent treatment with an MEK inhibitor and a PI3 kinase inhibitor, a drug combination currently being investigated in ongoing clinical trials.

    Source: AACR

  • Screening Blood Samples for Cancer-driving Mutations More Comprehensive Than Analyzing Traditional Tumor Biopsy

    Using a tool called BEAMing technology, which can detect cancer-driving gene mutations in patients’ blood samples, researchers from Dana-Farber Cancer Institute and Harvard Medical School showed that were able to identify oncogenic mutations associated with distinct responses to therapies used to treat patients with gastrointestinal stromal tumors (GIST).

    Source: AACR

  • More Accurate Markers Identified for Detecting Response to Epigenetic Drugs for Myelodysplastic Syndromes

    Researchers from the University of Southern California, Los Angeles, have identified and validated two DNA methylation markers that could help physicians better determine a patient’s response to DNA methyltransferase inhibitors (DNMTi) for the treatment of myelodysplastic syndromes (MDS).

    Source: AACR

  • Cohort Study Indicates That Selenium May Be Protective Against Advanced Prostate Cancer

    According to a data presented by researchers from Maastricht University in the Netherlands, a greater level of toenail selenium is associated with a significant decrease in the risk for advanced prostate cancer.

    Source: AACR

  • Comprehensive Genomic Analysis Identified Alterations in Head and Neck Cancer That Could Lead to Targeted Therapy

    A National Institutes of Health project to catalog the genetic alterations responsible for several types of cancer, in particular those with a poor prognosis, finds that head and neck squamous cell carcinomas are genomically heterogeneous. However, those cancer with certain distinctive patterns could be amenable to specific targeted therapies.

    Source: AACR

  • Novel Drug Combination Showed Antitumor Activity in Patients With Incurable BRCA-deficient Cancers

    Researchers from Dana-Farber Cancer Institute and Harvard Medical School have identified two orally available experimental drugs — sapacitabine and seliciclib — from phase I trial data that, when given sequentially, work together to elicit antitumor effects in patients with incurable BRCA-deficient cancers.

    Source: AACR

PerkinElmer Introduces New Chemical Intelligence Capabilities for Accelerating the Lead Discovery Process

PerkinElmer, Inc., a global leader focused on improving the health and safety of people and the environment, is introducing the newest version of Lead Discovery for the TIBCO Spotfire® software platform at the Company’s Revolutionaries for Global Health Summit. The new functionality of Lead Discovery 5.1 combined with the TIBCO Spotfire® software’s advanced data visualization and analysis capabilities bring a new level of chemical intelligence to the informatics platform for advanced scientific discovery.

PerkinElmer’s Lead Discovery™ 5.1 enhances the TIBCO Spotfire® software data analysis capabilities with new functionality built specifically with chemists in mind. Based on PerkinElmer’s industry-leading ChemDraw® drawing tool, the chemical intelligence in Lead Discovery provides scientists using TIBCO Spotfire® software with extensive chemical structure searching and visualization. Now scientists are able to dynamically filter their experimental data sets by chemical structure and pinpoint promising structural features and scaffolds in the output from their medicinal and combinatorial chemistry programs. The new technology enables users to mine their chemical databases to identify more compounds that have similar chemical structures, broadening their potential pool of candidates based on known properties and shortening their time to discovery of a viable candidate or lead.

“Through our relationship with TIBCO we are able to expand the range and depth of the TIBCO Spotfire® platform to serve the rapidly evolving needs of the scientific research community,” said Michael Stapleton, general manager, PerkinElmer Informatics. “With Lead Discovery 5.1, chemists will be able to explore their data sets in the context of visual chemical structures and as a result quickly filter to find the chemical compounds that are most promising to them. This capability will help them gain the critical insights they need to accelerate decisions on which compounds to pursue, while significantly reducing many of the typical technical bottlenecks to understanding data.”

In addition to dynamic, structure-based filtering, another key functionality of Lead Discovery 5.1 is that it automatically analyzes and displays R-groups (group side chains in chemical structure diagrams) or substituent variations on similar chemical scaffolds. These chemical variations have significant impact on dose response and side effects as they affect how the molecule interacts with a target. Using the new informatics tool, scientists can quickly isolate the variables to identify and optimize promising compound candidates.

“I foresee Lead Discovery becoming a heavily utilized aspect of our discovery scientists’ use of the TIBCO Spotfire® software,” said Dr. Daniel C. Weaver, manager of scientific computing at Array BioPharma Inc. “The capability to perform structure filtering and R-group analysis in real time will help drive compound series prioritization and structure activity relationship (SAR) analysis. This is critical to narrowing down the range of compounds that we are evaluating and helps to accelerate our ability to find the most promising candidates for our research.”

The Revolutionaries for Global Health Summit is PerkinElmer’s annual forum for leading researchers and physicians to network and share best practices in both science and business and participate in cutting-edge discussions to help lead to better prevention, detection and treatment of disease. At the Summit, several important presentations will be made by renowned users of the TIBCO Spotfire® software, and a hands-on workshop will allow attendees to learn how the software can impact their own research.

PerkinElmer leverages its deep scientific knowledge and expertise in the development of the most comprehensive suite of scientific informatics and software solutions – from instrument generated data, to enterprise solutions to mobile applications. Built by scientists for scientists, PerkinElmer’s integrated business-wide information management system provides companies and academic institutions with the necessary tools to aggregate, search, mine, analyze and visualize critical data so that they can turn data into actionable insights in an automated, predictive and scalable way. For more information, visit www.perkinelmer.com/informatics

Source: PerkinElmer

University of Maryland Medical Center Launches Genetic-Testing Program For Cardiac Stent Patients

Patients with coronary artery disease who undergo treatment at the University of Maryland Medical Center now can receive long-term therapy based on information found in their genes. As part of a new personalized medicine initiative, the medical center is offering genetic testing to help doctors determine which medication a patient should take after a stenting procedure in order to prevent blood clots that could lead to serious – and potentially fatal – heart attacks and strokes.

Patients with suspected heart disease undergo coronary catheterization to identify blocked or narrow arteries. Tiny tubes, or stents, are often placed in the arteries to keep them open, and, after surgery, patients typically take antiplatelet drugs, such as clopidogrel (Plavix), to prevent platelets – blood cells produced in bone marrow – from sticking together and forming clots.

Now, patients who undergo coronary catheterization at UMMC and the Baltimore VA Medical Center, both of which are affiliated with the University of Maryland School of Medicine, can elect to be tested for variations in a gene called CYP2C19. Up to one-fourth of the U.S. population carries at least one abnormal copy of the CYP2C19 gene, and research has shown that as a result, these individuals do not metabolize the standard anti-clotting medication clopidogrel effectively.

“There is strong clinical data to support pharmacogenetic testing in regard to antiplatelet therapy,” says Alan R. Shuldiner , M.D., the John L. Whitehurst Endowed Professor of Medicine, associate dean for personalized medicine and director of the Program in Personalized and Genomic Medicine at the University of Maryland School of Medicine. “It’s time to incorporate genetics into the complex medical decisions that we make on behalf of our patients.”

In 2009, Dr. Shuldiner led a University of Maryland study, published in JAMA, which showed that patients with a CYP2C19 gene variation exhibited reduced clinical benefit from taking clopidogrel. Based on growing clinical evidence reported in Dr. Shuldiner’s study and others, the U.S. Food and Drug Administration issued a warning about the reduced efficacy of clopidogrel in people with the genetic variation.

“Pharmacogenetic testing enables us to tailor drug treatments to individual patients based on their unique genetic makeup, or genotype,” says Dr. Shuldiner, an endocrinologist and geneticist. “With genotype-directed therapy, we have the ability to change the ‘one size fits all’ approach to prescribing medication and ultimately improve the quality of care we provide to our patients. Patients want personalized and individualized medicine. They seek it out.”

The test is performed by analyzing the patient’s DNA, isolated from a blood sample, in a new state-of-the-art translational genomics laboratory at the University of Maryland School of Medicine. The tests are being conducted as part of a National Institutes of Health (NIH)-funded study to determine the best way to implement genetic-testing programs. Tests are free, and because of the partnership between UMMC and the University of Maryland School of Medicine, results are available within a few hours.

Dr. Shuldiner explains that the ability to provide test results within hours is crucial because cardiac stent patients are at risk for developing blood clots and other complications soon after they have the procedure. “This rapid turnaround time sets our program apart from other programs and commercial laboratories, where results may not be available for up to two weeks,” he adds.
Pharmacogenomics – how genes affect a person’s response to drugs – is a burgeoning area of research, but only a small number of hospitals in the United States have programs to offer routine genetic testing as part of their clinical practice. This new approach to patient care is part of the University of Maryland School of Medicine’s pursuit of more individualized, or personalized, medical treatment.

E. Albert Reece , M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine, says, “Personalized medicine is the future of health care, and we want to be at the forefront of not only advancing the science of genomics, but also using that knowledge in a clinical setting for the benefit of patients. Our Program in Personalized and Genomic Medicine, under Dr. Shuldiner’s direction, is helping to lead the way with this new genetic-testing initiative, created in partnership with the University of Maryland Medical Center and the Baltimore VA Medical Center.”

The University of Maryland launched its initiative in conjunction with a multi-center implementation study, the Translational Pharmacogenetics Project, funded by the NIH Pharmacogenomics Research Network (U01HL105198). Five other major hospitals across the United States are taking part in the study to evaluate the process for building such pharmacogenetic-testing programs.

“We plan to share lessons learned at our respective sites and to develop best practices for implementation of pharmacogenetics in everyday clinical practice. We are putting together a toolbox that will be useful to other institutions,” says Dr. Shuldiner, who is leading the multi-center study. Cardiologists Mark R.Vesely , M.D., and Shawn W. Robinson , M.D., assistant professors of medicine at the School of Medicine who care for patients at UMMC and the Baltimore VA Medical Center, are co-investigators.

It is expected that the test for the CYP2C19 gene variation will become standard care for all patients who receive stents at both medical centers once the initial research phase is completed.
Cardiologists receive guidelines on how to interpret the test results and recommendations for choosing medications. It is up to them to determine the most appropriate treatment for their patients, who might have other medical conditions that need to be considered. The test results also are entered in the electronic medical record, where they can be accessed by other physicians.

“Knowing a patient’s genotype is helping us to make more informed decisions for our patients,” Dr. Vesely says. “A combination of aspirin and clopidogrel is the routine choice of medications many physicians will prescribe for their stent patients. But patients who are likely to have a poor or moderate response may be better protected by other medications or possibly a higher dose of clopidogrel. It comes down to what is best for each patient.”

According to Dr. Vesely, limitations for the alternative medications include their association with higher bleeding rates. “The cost of the medications could also be a factor if patients cannot afford alternative medications or will not take them as prescribed.” Newer anti-clotting medications, such as prasugrel (Effient) and ticagrelor (Brilinta), are more expensive than Plavix, which has been available as a generic since May 2012.

Dr. Robinson notes that the response from patients to genetic testing has been positive. “Patients have been very receptive to discovering this new information about themselves that can possibly have a positive impact on their future cardiovascular health,” he says.

Dr. Shuldiner anticipates that the initiative will be expanded to include tests for other genes that may affect how patients respond to medications such as warfarin, an anticoagulant; simvastatin, a cholesterol-lowering drug; and codeine, a pain reliever. “Providing tailored therapy will better meet the health needs of patients and reduce the harmful side effects that can occur when a person is taking the wrong medication,” he says.

The University of Maryland School of Medicine’s Personalized and Genomic Medicine Program was established in April 2011 to help facilitate the pace of discovery in personalized and genomic medicine; to accelerate the translation of these new discoveries to improve patient care; and to enhance the training and education of future generations of physicians and scientists. The program is funded jointly by the School of Medicine and University of Maryland Medical Center.

To watch a video of Dr. Shuldiner discussing the new initiative, go to http://www.umm.edu/media/channel/heart-cardiovascular.htm.

Source: PR Newswire