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Biomarker Assessment in Suspected ACS Could be Practice-changing: BIC-8 Results

An emergency department strategy that uses two biomarkers to triage patients with suspected acute coronary syndrome (ACS) can increase the rate of early, safe hospital discharge, according to results of the Biomarkers in Cardiology 8 (BIC-8) trial.

“This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety,” said lead investigator Martin Möckel, MD, PhD, from Charité – Universitätsmedizin Berlin, in Berlin, Germany.

“This is the first interventional trial to study whether it is safe to discharge suspected ACS patients who test troponin and copeptin negative at admission. Using this strategy, a high proportion of patients could be discharged early, thus unnecessary treatments and resources could be saved, causing a substantial benefit for patients and health care providers.”

Emergency departments worldwide face increasing overcrowding and patients with signs and symptoms which might be caused by an acute coronary syndrome are very common, even though only around 15% of these patients are ultimately diagnosed with an acute myocardial infarction as the underlying disease, explained Dr. Möckel.

“Rapid rule-out of acute myocardial infarction (MI) is therefore a major clinical need, saving the health care system time and resources and patients unnecessary stress, anxiety and other risks associated with hospitalization.”

Current guidelines recommend that patients receive serial troponin testing to confirm that hospital discharge is appropriate, but this testing delays definitive action, he said.

“The new biomarker copeptin has been shown to be elevated in patients first presenting with acute MI, and when combined with the cardiac troponin biomarker has an excellent negative predictive value for acute MI. However, an early discharge strategy based on combining these two tests has never been assessed prospectively.”

BIC-8, a multicentre, open, randomized, controlled clinical trial included 902 patients with an initial negative troponin test to assess this strategy.

In the experimental arm (n=451), patients with a negative copeptin test (less than 10 pmol/L) were discharged into ambulant care, with a scheduled outpatient visit within 72 hours, while those with a positive copeptin test received standard treatment according to current guidelines.

Among patients in the standard arm (n=451), copeptin results were not available to treating staff and patients were treated according to current guidelines.

At 30 days of follow-up the rate of major adverse cardiovascular events (MACE) was similar in both groups (5.46% in the experimental arm vs 5.5% in the standard arm), but emergency room discharge rates were significantly higher in the experimental arm (66% vs 12%; P < 0.001).

The results support the consideration of a new treatment algorithm in low-to-intermediate risk patients with suspected ACS, said Dr. Möckel.

“Patients with a negative troponin and a negative copeptin result at admission can safely be discharged if the final clinical assessment is consistent with this decision, as long as a timely diagnostic work-up is done in the outpatient setting,” he said.

However, the clinical judgment of the treating physician is of utmost importance, he stressed.

“If his or her final clinical assessment excludes discharge due to high suspicion of ACS, perhaps due to recurrent symptoms or an updated history, the patient should not be discharged despite negative biomarker results.”

Source: EurekAlert!

EMD Serono Establishes Immuno-Oncology Research and Early Development Platform to Advance Innovation in Cancer Therapies

EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany, recently announced its commitment to the field of cancer immunotherapy by creating a fully dedicated immuno-oncology innovation platform integrating research, early development and biomarker strategies. In addition to the company’s existing oncology platform, this new immuno-oncology platform will focus on developing therapies that leverage the immune system’s natural ability to fight tumors, and work in combination with existing and future therapies.

“We are pleased to announce our commitment to immuno-oncology, recognizing that the complexity of cancer requires diverse approaches that will enable alternative therapeutic interventions,” said Bernhard Kirschbaum, Head of Global Research and Early Development at Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “In order to spur research and early development in this specialized area, we have created an innovative environment where researchers and clinicians work side-by-side to advance potential new cancer immunotherapies.”

The new immuno-oncology platform includes three innovation clusters, each of which is focused on discovery research and the advancement of molecules into the clinic through proof of confidence:

  • Therapeutic cancer vaccines: targeting tumor antigens to elicit a tumor-specific immune response
  • Cancer stem cells: targeting cancer stem cells to prevent or reduce tumor formation and inhibit metastases
  • Immunotolerance: eliminating or circumventing inhibitory mechanisms in the immune system that prevent cancer cells from being recognized and attacked by the body

To ensure a broad immuno-oncology research and early development platform, EMD Serono has assembled an in-house team of preeminent researchers and clinicians who will focus resources and technologies to build a portfolio of investigational immunotherapies, while collaborating with premier academia, research and industry organizations to complement internal capabilities.

The current immuno-oncology portfolio comprises therapeutic candidates in early clinical development and a robust pipeline of pre-clinical molecules. Leading therapeutic concepts in the clinic are:

  • A monoclonal antibody targeting PD-L1 (programmed cell death ligand) expressed by various tumors, currently in Phase I in solid tumors
  • NHS-IL12, a cancer immunotherapy targeting IL-12 to the necrotic regions of tumors, sponsored by the United States National Cancer Institute (NCI), currently in Phase I in solid tumors
  • NHS-IL2, targeting IL-2 to the necrotic regions of tumors, completed Phase I and currently preparing for Phase II in solid tumors

“Our goal is to develop leading immunotherapies that work in combination with other therapeutic modalities, understanding that attacking multiple cancer targets simultaneously increases the possibility of therapeutic success,” said Helen Sabzevari, Head of Immuno-Oncology, Global Research and Early Development at Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “We are committed to delivering on the promise of immuno-oncology by combining creative thinking with strong research and clinical excellence, and, more importantly, by keeping patient needs at the heart of our efforts.”

Source: EMD Serono

No Biomarkers Identified to Assess Potential Health Effects of GMOs

Many people in Europe are critical of genetically modified (GM) food, due to safety concerns. A Eurobarometer survey, published in 2010, revealed that the European public tends to be worried on a “mediate level” about GM food, with people in Austria being particularly concerned. Today, genetically modified maize is cultivated commercially, mainly in Spain and Portugal. Nonetheless, authorised GM Organisms (GMO) may enter the European market as feed for animals or in food products.

Whether such products pose any health threats to consumers, is controversial. “We have to find the best way to evaluate the issue,” says Michelle Epstein, an allergy and immunology clinician from the Medical University of Vienna, Austria. She coordinated a recently completed EU-funded project called GMSAFOOD that aimed at identifying possible biomarkers for indicating adverse health effects of GM food. Such biomarkers could be used for monitoring commercially available GM food or feed.

The European Food Safety Authority EFSA, who plays a fundamental role in assessing the risk of GM crops and derived food and feed in Europe, has included a recommendation for so-called post-market monitoring (PMM) in its Guidance for risk assessment of food and feed from genetically modified plants, published in 2011. This approach is supposed to complement the pre-market toxicological tests. “This [the PMM] is for the unexpected things”, Epstein explains. “Even if you do a lot of testing before placing a product on the market, it is not the public at large you are testing,” she tells youris.com. Some people may have immune diseases or consume certain products at very high levels.

As part of the project, the researchers conducted feeding experiments with pigs, mice, salmon and rats. They fed them with a variety of commercially available GM maize, called MON 810, and a pea containing a pest resistance gene derived from a bean. “We were using the peas because we knew it had effects”, Epstein says. Indeed, a previous study published in 2005 by Australian scientists had shown allergenic responses in mice feeding on the pea.

However, the researchers were not successful in their search for biomarkers. “We didn’t see any health effects”, Epstein comments. Moreover, when looking at the allergenic effect the peas had caused in the original study, the scientists found the same effects in the native bean, implying that the GM pea did not cause the allergic reaction. They attributed this discrepancy to a cross-reaction with a substance called pea lectin and to technical differences between testing laboratories.

The project scientists also developed a machine learning approach to identify potential GMO-associated biomarkers. Data is fed into a mathematical model, which is supposed to find parameters that may serve as biomarkers. “We proposed to the [European Commission] to set up a public repository with all of the project data,” Epstein says. This public database would also allow people from research and industry to include their own data and use the approach for identifying biomarkers for PMM.

Experts doubt the usefulness of PMM, in this case. “In my view, in contrast to the mandatory post-market environmental monitoring, monitoring GM food is questionable,” comments Joachim Schiemann, biosafety expert at the Julius Kühn-Institut, Federal Research Centre for Cultivated Plants, Germany. He considers the pre-market risk assessment of GM food as sufficient in most cases. He argues that uncertainties should be defined prior to introducing a product to the market. “The regulatory authorities have to decide how much uncertainty is acceptable,” Schiemann adds.

Other experts agree. “I am personally very reluctant to consider PMM as a useful tool for risk management of GM food or feed,” Harry Kuiper, retired scientist at Wageningen University, the Netherlands, and former head of the GMO Panel at EFSA, says. He points at various difficulties PMM may face. For example, he believes that it is hard to determine which group to target and how much of a product people actually consume.

“For the GM foods on the market today, there are simply no indications for identification of biomarkers upon exposure of humans or animals,” Kuiper also tells youris.com. “Personally, I would try to solve problems or uncertainties identified with GM food or feed during the pre-market risk assessment”, he adds. However, he believes that future GM food, which may alter the physiological or nutritional status of humans or animals, may provide opportunities for identifying biomarkers.

While she is not opposed to post-market monitoring, Helen Wallace, director of the not-for-profit organisation Genewatch UK recognises that “it is a very hard thing to do”. Instead, “we need more pre-market assessments of GM crops”, Wallace says. In her view, these should include follow-ups of studies, which suggest possible adverse health effects. She also criticises prevalent study designs and the fact that regulators have to rely on commercial studies: “These lack independence and often data isn’t made public by companies.”

Source: Youris.com

Luminex Corporation and EMD Millipore Extend Their Global Supply and Distribution Agreement

Luminex Corporation (NASDAQ: LMNX) recently announced it has extended their global supply and distribution agreement with EMD Millipore—the Life Science division of Merck KGaA, Darmstadt, Germany. This long-term agreement strengthens the partnership and facilitates development of life science and protein assays by EMD Millipore for Luminex’s flexible platform.

AgedBrainSYSBIO, a Medium-scale Research Initiative Against Neurodegenerative Diseases

The AgedBrainSYSBIO project on systems biology of synapse proteins & ageing was officially launched recently in Paris, France. AgedBrainSYSBIO is a European collaborative research project funded by the European Commission under the Health Work Programme of the 7th Framework Programme. This multidisciplinary consortium assembles 14 academic and industrial internationally renowned research teams from Belgium, Estonia, France, Germany, Israel, United Kingdom and Switzerland.

Ageing is undisputedly a complex process because it affects the deterioration of most (if not all) aspects of life. Cognitive decline is emerging as one of the greatest public health challenges of the old age, with nearly 50% of adults over 85 afflicted by Alzheimer’s disease, the most common type of dementia.

As other chronic and neurodegenerative diseases, Alzheimer’s disease develops slowly and gradually; but is distinctive in that it forces patients to endure many years of steadily-lessening contact with others, because of memory loss, difficulty with orientation, loss of language and speaking abilities, judging things and depression amongst numerous other symptoms. In 2013, it is estimated that there are worldly more than 24 million people with Alzheimer’s disease, with 4.6 million new cases each year, which means a new case each 7 seconds. It is thus one of the greatest challenges in public health for modern societies, in terms of costs but also in terms of cause, cure and care. To address all these issues, European Commission-funded research effort is crucial as there are still no curative drugs, with only symptomatic treatment able to delay the disease progression.

Over the last years, Genome-Wide Association Studies (GWAS) have been instrumental to identify genes that mediate genetic risk associated to Late-Onset Alzheimer Diseases (LOAD). These approaches based on the genetic comparison of large cohorts of patients and healthy aged persons, and for which three academic partners have been involved (Inserm U894; Institut Pasteur Lille, University of Antwerpen), have been largely funded by Europe. Additionally, a variety of new sets of data have been built and have delivered the state-of-the art of protein-protein interactions, their localisation in subregions of human neurons and genome-wide transcriptome analysis of human neurons derived from aged patient fibroblasts. In another field, new drosophila and mouse models have been also generated via academic partners involved in European Commission-supported large-scale programmes. Finally, the analysis of genes displaying an accelerated evolution in humans as non-human primates do not display these human-specific neurodegenerative diseases has open interesting research paths. So far however, in spite of a huge amount of data available and existing in vitro and in vivo models, these approaches have not been successfully translated into the clinic separately.

The AgedBrainSYSBIO will take advantage of these large set of data, will cross them to other large-scale ageing databases and will include all of these know-how, technologies and results. Thanks to the involvement of four European SMEs, this program is expected to get results readily translated into preclinical studies.

AgedBrainSYSBIO project assembles 13 well-established research teams both from academia and industry. The scientists will share results and know how on LOAD GWAS gene discovery, comparative functional genomics in mouse and drosophila models, in mouse transgenic approaches research on human induced pluripotent stem cells (hiPSC) and their differentiation in vitro and modelling pathways with emphasis on comparative and evolutionary aspects. Importantly, the four European SMEs involved will bring their complementary expertise. QURETEC (Estonia) will be a key partner for data management solutions and bioinformatics data analyses; HYBRIGENICS (France) is a world leader in comparative proteomics and protein-protein interaction analyses; GENEBRIDGES (Germany) is marketing novel strategies for DNA engineering in mammalian cells; reMYND (Belgium) is a leader for development of protein misfolding-modifying treatments against LOAD .

Together, researchers will address the basis of brain ageing by studying the pathways involved in Late-Onset Alzheimer Diseases combining integrative systems biology and comparative genomics. One of the first steps will be to identify the interactions through which the ageing phenotype develops in normal and in disease conditions; on this basis, novel pathways and their evolutionary properties will be modelled and experimentally tested in order to identify druggable targets. This work will finally allow the validation of new druggable targets and markers as a proof-of-concept towards the prevention and cure of aging cognitive defects.

Michel Simonneau, MD PhD, Professor at Ecole Normale Supérieure de Cachan, who coordinates this effort states that “this ambitious project integrates the numerous European initiatives, such as JPND , as well as national research programmes, which addresse the scientific and societal challenge of neurodegenerative diseases. This project receives the decisive input of 4 small to medium size enterprises (SMEs) that allow us to get candidate solutions for curing and preventing common age-related diseases. The links between academia and industry is the driving force of this work programme and in the end will hopefully benefit to all of us.”

Source: EurekAlert!