Biomarker research has moved on from proteins to nucleic acids where one of the main priorities is the use of microRNA expression profiles. The Heidelberg-based biotech company Comprehensive Biomarker Center GmbH (CBC, formerly febit) has state-of-the-art technologies and the skills and knowledge to advance the development of new nucleic acid biomarkers for complex diseases in cooperation with partners from research and industry.
This company is in the described form no longer active in the market.
The European Medicines Agency (EMA) is convinced that the development of new therapeutics will increasingly be determined and driven by diagnostic and prognostic biomarkers. In August 2011, the EMA published a draft reflection paper on the healthcare market of the 21st century. The paper was sent to European pharmaceutical companies who had until the end of November 2011 to make comments. Although all the big pharmaceutical companies highlight the importance of biomarkers, some companies are nevertheless reluctant when it comes to the strategic revision of their development concepts for new drugs, mainly because of the fear of having to give up familiar and lucrative blockbuster models for new nichebuster ones, which may lead to a drastic decrease in profit. Supporters of the new model are convinced, however, that scientific progress towards biomarker-driven drug development is not just a matter of patient well-being, but also of potential economic rewards.
The priorities of biomarker research in academic settings have shifted in the last few years from proteins to genomic analysis and gene expression. This is a result of massive technological progress that has greatly reduced the time and costs associated with DNA sequencing. Despite the advantage of what are known as next-generation sequencing technologies (NGS), leading diagnostics companies have been quite hesitant to jump on the bandwagon. The major reason for their reluctance is the enormous sums of money they have already invested in the development of protein biomarkers. Another major argument for not becoming involved is that proteins are generally regarded as molecules that determine a person's phenotype; disease-related changes, it is believed, show more accurately in proteins than on the genetic level. However, this argument has lost its persuasive power following improvements in gene expression analysis and RNA sequencing for transcriptome analysis.
Based on the notion that cancers occur due to abnormalities in DNA, the identification of cancer biomarkers is largely based on DNA analysis, as the International Cancer Genome Project and other projects have shown. However, today's disease biomarker research also involves the analysis of RNA. microRNAs, small non-coding RNA molecules discovered only around ten years ago, are a particularly hot topic as they have since been identified as regulatory elements for messenger RNA (mRNA). Not a week goes by without the application of microRNA for disease diagnosis appearing in the news.
The Heidelberg-based biotechnology company febit, a specialist in the analysis and synthesis of nucleic acids, focused at a very early stage on the huge medical application potential of nucleic acid biomarker research. febit was the driving force behind the establishment of a "Biomarker Discovery Center" in Heidelberg, which has recently coordinated a large Germany-wide study that showed that it was possible to use microRNA profiles of patient blood samples for the early diagnosis of cancer and other diseases (BIOPRO article entitled "Krebsdiagnostik durch microRNAs im Blut").
febit was also involved in the BioRN Biomarker Center, one of several large cooperative projects carried out by the BioRN cluster. The BioRN Biomarker Center brings together companies and research institutions with the aim of characterising molecular biomarkers for the development of new diagnostic tools. As part of comprehensive operational restructuring measures in summer 2010, febit shifted its strategic focus towards the discovery and validation of blood-based microRNA biomarkers in cooperation with partners from clinical research and the diagnostics and pharmaceutical industries. As a consequence of its new strategic focus, febit was renamed "Comprehensive Biomarker Center GmbH (CBC).
According to the current state of research, diseases are not characterised by specific microRNA molecules, but by microRNA profiles, i.e. different patterns of the composition and proportions of many different microRNAs. The particular advantage of microRNAs in clinical practice is the fact that they are relatively stable molecules: the specific disease-related expression profiles (signatures) remain intact in formalin-fixed, paraffin-embedded tissue samples as well as in the majority of body fluids and secretions (blood, plasma, serum, urine, saliva, pleural and amniotic fluid). Many papers published over the last few years highlight the huge potential of microRNA analyses of patient samples (e.g. peripheral blood or blood cells) for the non-invasive diagnosis of cancer and certain autoimmune and inflammatory disorders. In addition to the aforementioned large multicentre study on different tumours, CBC was also involved in studies on the application of microRNA for the diagnosis of multiple sclerosis and acute myocardial infarction. CBC offers its comprehensive experience in the preparation and bioinformatic analysis of microRNA signatures in pathologically altered situations to cooperation partners in hospitals and industry working on biomarker studies. CBC has a database of more than 4,000 microRNA profiles derived from patient body fluids. CBC’s microRNA profiles cover a broad range of different diseases, including cancer and inflammatory, infectious and cardiovascular diseases.
It goes without saying that the reliable diagnosis of diseases also needs to take into account other parameters. Many diseases are characterised by genetic factors that affect disease progression and therapeutic outcome. Genomic biomarkers have been found to be excellent tools for monitoring disease progression and therapeutic outcome. For example, the DNA found in the body fluids of patients with systemic inflammatory diseases such as multiple sclerosis reveals genetic and epigenetic alterations that are characteristic of a certain disease or stage of disease. With its huge experience in nucleic acid analytics, in particular in next-generation sequencing, CBC is able to offer its clients analyses of DNA methylations as well as exome sequencing. The exome is the part of the human genome that codes for proteins and other functional products. It only constitutes a small fraction of the entire human genome, but has been found to be the cause of the majority of human genetic diseases.
Another highly promising approach is the analysis of the transcriptome, i.e. the RNA of all transcribed genes. Since the transcriptome depends on the physiological and pathological state of cells, mRNA signatures have the potential to be used as biomarkers for specific disease states. For example, disease-associated mRNAs of mononuclear or peripheral blood cells (lymphocytes and monocytes) have been identified in patients with rheumatoid arthritis and chronic inflammatory diseases and used for the molecular classification of bowel diseases such as Crohn's disease and ulcerative colitis. CBC offers a broad range of services for biomarker studies on the transcriptome level, including the detection of single RNA molecules by way of coding and non-coding sequences, splicing and mutation analyses and the accurate quantification of the entire transcriptome.
Reference:Keller A., et al. 2011: Toward the blood-borne miRNome of human disease. Nature Methods, doi: 10.1038/nmeth.1682
Further information:Comprehensive Biomarker Center GmbH (CBC)Im Neuenheimer Feld 51969120 HeidelbergTel.: +49 (0)6221/ 6510 - 300Fax: +49 (0)6221/ 6510 - 329E-mail: info(at)cbioc.com