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COPD Biomarker Qualification Consortium Making Strides with Plasma Fibrinogen as New Biomarker

The COPD Biomarkers Qualification Consortium (CBQC) recently announced at the European Respiratory Society Annual Congress that it has submitted a Qualification Package to the Food and Drug Administration (FDA) for plasma fibrinogen as a new drug development tool. The Qualification Package is the result of progressive discussions between the FDA’s Qualification Review Team and the CBQC. The CBQC looks forward to the results of FDA review while planning for a fall 2013 submission to the European Medicines Agency.

Dr. Ruth Tal-Singer, CBQC co-chair, vice president, Clinical Discovery, Respiratory Area Therapy Unit at GlaxoSmithKline, notes, “To the best of CBQC’s knowledge, fibrinogen is the first clinical biomarker achieving this milestone in the U.S. This is a major milestone for the CBQC, and it highlights the power of working together across multiple companies, academic centers and government organizations to achieve our common objective of improving the way we study novel medicines for patients who need them.”

To support the submission, the CBQC compiled a unique database of subjects from five individual studies, allowing integrated analyses to support two proposed uses as a prognostic biomarker to enrich clinical trial populations with Chronic Obstructive Pulmonary Disease (COPD) subjects at increased risk for all-cause mortality or COPD exacerbations.

A biomarker is a tool that can be used for early detection of a disease, selection of subjects for clinical trials or as an outcome for clinical trials. Fibrinogen, a protein that can be measured in the blood, is a promising biomarker which identifies a group representing 25 to 30 percent of all COPD patients (a COPD subtype).

Dr. Stephen Rennard, CBQC co-chair and Larson Professor of Medicine, University of Nebraska, adds, “COPD is extremely heterogeneous. This complicates development of new treatments, as individual COPD patients may respond differently. Fibrinogen has been submitted to the FDA as a tool that will help address this problem. Specifically, fibrinogen measurement can help identify COPD patients at risk for death or hospitalization, which can allow individuals to participate in studies of novel treatments designed to improve those outcomes.”

The CBQC, organized under the auspices of the COPD Foundation, is a public-private partnership among academic researchers, pharmaceutical companies and government parties and agencies.

John W. Walsh, president and co-founder, COPD Foundation, states, “The Consortium is providing a unique and productive opportunity to bring new drug development tools to the research community, with the ultimate goal of providing new treatments to patients who urgently need them.”

The CBQC Fibrinogen Working Group is composed of the following members:

  • Bruce Miller, industry co-chair, GlaxoSmithKline
  • Ruth Tal-Singer, GlaxoSmithKline
  • Mike Lowings, GlaxoSmithKline
  • Ubaldo Martin, AstraZeneca
  • Jeff Snyder, Boehringer-Ingelheim
  • Kay Tetzlaff, Boehringer-Ingelheim
  • Armin Furtwaengler, Boehringer-Ingelheim
  • Nicholas Locantore, GlaxoSmithKline
  • Nancy Leidy, Evidera
  • Amber Martin, Evidera
  • Jason Simeone, Evidera
  • David Mannino, academic co-chair, University of Kentucky
  • Stephen Rennard, University of Nebraska
  • David Lomas, University College London, U.K.
  • Jorgen Vestbo, University of Southern Denmark, University Hospital Manchester, U.K.
  • Graham Barr, Columbia University
  • Debora Merrill, COPD Foundation

Source: COPD Foundation

Almac Offering TruSight Tumor Profiling Next-Generation Sequencing Service

Almac recently announced they are now offering a Tumor Profiling service running Illumina’s next-generation sequencing (NGS) TruSight Tumor™ panel as part of their biomarker discovery, development and delivery solutions.

Almac, a personalised medicine company with CAP accredited and CLIA certified laboratories, extends their portfolio of services by offering TruSight Tumor™ to complement its current range of RNA, DNA and protein based technologies for biomarker analysis.

Almac is currently running many bespoke diagnostic assays for pharma customers for early phase clinical trial enrichment. The TruSight Tumor™ panel enables additional profiling of these patient samples to provide Almac’s pharma partners with further important information on emerging biomarkers that may also impact drug response.
The TruSight Tumor™ panel was developed by Illumina for their MiSeq® system, allowing targeted DNA sequencing and reporting on the mutation status of 26 genes which are most commonly mutated in solid tumors including lung, colon, ovarian, melanoma and gastric cancers.

One of Almac’s key strengths is many years of experience in working with formalin fixed paraffin embedded (FFPE) tissue. The TruSight Tumor™ panel is specifically designed for use with FFPE samples, and enables the highest levels of sensitivity for mutation detection with limited DNA input requirements.

“Almac is committed to the development of personalised medicine through the delivery of a wide range of innovative solutions. We are pleased to announce the expansion of our NGS service to include TruSight Tumor™” said Professor Paul Harkin, President and Managing Director of Almac’s Diagnostic business unit.

Source: Almac

Researchers to Identify Genetic Biomarkers for Aggressive Breast Cancer

The Avon Foundation for Women recently awarded a $300,000 grant to Dolores Di Vizio, MD, PhD, associate professor in the Department of Surgery and the Department of Pathology and Laboratory Medicine and a member of the Cancer Biology and Urologic Oncology Research Programs at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute to advance scientific research in aggressive breast cancer.

Di Vizio will collaborate with the Cedars-Sinai Women’s Cancer Program to investigate biomarkers in patient blood samples that may identify individuals with aggressive breast cancer. Biomarkers are genes or other molecules that can indicate a person’s predisposition to specific medical conditions.

Research findings have the potential to create a novel standard of care and a new source of biomarkers. The possible new source of biomarkers, known as large oncosomes, are tumor-derived vesicles that transmit signaling complexes between cell compartments, providing valuable insight into the progression of disease. Findings may also help researchers and clinicians predict the aggressiveness of breast cancer earlier in the diagnostic process.

“This kind of research is the essential foundation to get us to our real goal, which is to improve diagnostic and prognostic capabilities and find effective treatments for breast cancer,” said Di Vizio. “With this study, we hope to identify previously unrecognized large oncosomes as potential biomarkers in advanced tumors that can be visualized, quantified and isolated using methods easily translatable to the clinic.”

Funding from the Avon Foundation for Women, a nonprofit organization and longtime supporter of Cedars-Sinai, will provide an opportunity for researchers to further spearhead new technologies, therapies and surgical interventions that may provide better patient outcomes, beginning at diagnosis.

Working with Di Vizio to provide these advancements is collaborator Beth Y. Karlan, MD, director of the Women’s Cancer Program, director of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology, the Cedars-Sinai Board of Governors Chair in Gynecologic Oncology and the director of the Cedars-Sinai Gilda Radner Hereditary Cancer Program.

“I’m excited to be a collaborator on this research study, as it holds promise to provide tangible improvements in earlier diagnostics and detection in aggressive breast cancer and is perfectly aligned with the program goals of the Cedars-Sinai Women’s Cancer Program,” said Karlan. “This Avon Foundation for Women grant will further our program’s commitment to studying cancer biology, developing new approaches to early detection and preventing and improving cancer survival for all patients.”

This is the first study on large oncosomes analyses in patients with breast cancer. Pilot funding for this grant is supported by the Martz Breast Cancer Discovery Fund.

Source: EurekAlert!

New Workflow to Provide Scientists with Tools That Enable Single Cell Analysis for Oncology, Immunology and Stem Cell Research

NanoString Technologies, Inc. (NASDAQ: NSTG), a provider of life science tools for translational research and molecular diagnostic products, and BD Biosciences, a segment of BD (Becton, Dickinson and Company) (NYSE: BDX), a leading global medical technology company, recently announced a collaboration agreement for the development of a single cell isolation and analysis workflow.

Under the agreement, the companies will jointly develop a workflow using the NanoString nCounter®Analysis System (including the nCounter Single Cell Assay) and the BD Flow Cytometry cell sorter product line (emphasizing the new BD FACSJazz™ Cell Sorting System). The combined workflow will enable single cell gene expression analysis for research applications such as oncology, immunology and stem cell research. Collaboration activities will also include the development of materials documenting the workflow protocol, as well as co-hosting meetings and webinars to educate scientists about the single cell workflow.

“Maximizing both the quantity and quality of data that can be extracted from a single cell is critical to the emerging field of single cell biology. The nCounter Analysis System can analyze entire gene pathways and provides a highly precise and reproducible digital output, making it ideally suited to the task,” said Brad Gray, President and Chief Executive Officer, NanoString Technologies. “The nCounter Analysis System and the BD FACSJazz Cell Sorting System can together provide a powerful and efficient workflow for single cell gene expression analysis.”

“Our collaboration with NanoString Technologies furthers BD’s commitment to providing researchers advanced solutions for cell analysis and isolation,” said Alberto Mas, President, BD Biosciences. “We believe this new sorting workflow will complement the recent and very rapid advances in genomic studies that value the requirement for greater sample integrity for critical single cell analysis.”

NanoString Technologies’ nCounter Analysis System is a multi-application digital detection and counting system with a highly automated and simple workflow. The company’s Single Cell Gene Expression application provides researchers with a highly flexible and sensitive approach to discovering differences in cell-to-cell gene expression profiles.The application enables up to 800 genes to be detected in a single tube.

The BD FACSJazz Cell Sorting System is capable of identifying, characterizing and isolating single or multiple cells – from complex or extremely rare cell populations – and depositing them in 96 and 384 well plates to provide rapid cell isolation, tracking and identification throughout the process.

For more information about NanoString Technologies, the nCounter Analysis System and the nCounter Single Cell Assay, please visit www.nanostring.com.

For more information on the BD FACSJazz Cell Sorting System, please visit www.bdbiosciences.com/facsjazz.

Source: BD Biosciences

Droplet Digital PCR Enables Reproducible Quantification of microRNA Biomarkers

A study published online in Nature Methods recently demonstrated that Droplet Digital PCR (ddPCR™) technology can be used to precisely and reproducibly quantify microRNA (miRNA) in plasma and serum across different days, paving the way for further development of miRNA and other nucleic acids as circulating biomarkers.

“In the field of circulating microRNA diagnostics, droplet digital PCR enables us to finally perform biomarker studies in which the measurements are directly comparable across days within a laboratory and even among different laboratories,” said Dr. Muneesh Tewari, Associate Member in the Human Biology Division at the Fred Hutchinson Cancer Research Center and lead author of the study.

Challenges in miRNA quantification

miRNAs are small regulatory RNA molecules with diverse cellular functions. The human genome may encode over 1,000 miRNAs, which could target about 60 percent of mammalian genes. Because they are abundant in many cell types, exist in highly stable extracellular forms, and may provide direct information about disease processes, they are being actively studied as blood-based biomarkers for cancer and other diseases.

Quantitative real-time PCR (qPCR) has been used for the analytical measurement of miRNAs in blood samples; however, researchers have found that qPCR measurements of miRNAs in serum or plasma display unacceptably high interday variability, undermining the use of miRNAs as reliable blood-based biomarkers. An approach that yields more dependable results has therefore been sought by researchers in this field.

Advantages of ddPCR for miRNA detection

Digital PCR has many advantages over qPCR including the ability to provide absolute quantification without a standard curve and robustness to variations in PCR efficiency across different samples and assays. These and other advantages are embodied in Bio-Rad Laboratories’ QX100™ Droplet Digital PCR (ddPCR™) system, which was introduced in 2011.

“We chose to use Bio-Rad’s QX100 Droplet Digital PCR system because it was the first system on the market that could make digital PCR practical from a cost and throughput standpoint for routine use in the lab,” said Dr. Tewari.

To assess the imprecision introduced by each workflow step — serial dilution preparation, reverse transcription (RT), and PCR technical replicates — Dr. Tewari and his team conducted nested analyses of ddPCR vs. qPCR on cDNA from a dilution series of six different synthetic miRNAs in both water and plasma on three separate days. In comparison to qPCR, the researchers found that ddPCR demonstrated greater precision (48–72% lower coefficients of variation) with respect to PCR-specific variation

Next, the team performed a side-by-side comparison of qPCR to ddPCR for detecting miRNAs in serum. They collected sera samples from 20 patients with advanced prostate cancer and 20 age-matched male controls and measured the abundance of miR-141, which has been shown to be a biomarker for advanced prostate cancer. Samples were analyzed by qPCR and ddPCR with individual dilution series replicates prepared on three different days. They found that ddPCR improved day-to-day reproducibility seven-fold relative to qPCR. It was also able to demonstrate differences between case vs. control specimens with much higher confidence than qPCR (p=0.0036 vs. p=0.1199).

“Droplet digital PCR will allow us to accurately follow serum microRNA biomarker concentrations over time during a patient’s treatment course, something that has been nearly impossible to achieve with real-time PCR,” he said.

Study: Absolute quantification by droplet digital PCR versus analog real-time PCR [Nature Methods]

Source: EurekAlert!