Biomarkers are measured and evaluated as indicators of biological or pathogenic processes, or of pharmacological or toxicological responses. They include secreted proteins, as well as DNA and expression markers. Biomarkers hold the key to improving our understanding of the underlying biological triggers driving these processes.
Most of today's biomarkers were developed in the 1950s, and are primarily diagnostic. Little progress has been made in developing new and/or more sensitive indicators of injury and disease, and in particular, prognostic indicators.
As a result, there is a great deal of speculation around the notion of biomarker discovery - is the industry actually making progress identifying and applying biomarkers to improve healthcare? If not, what are the key barriers and do any solutions exist?
There has been considerable interest expressed by the industry in advancing biomarker discovery and validation, partly fuelled by the FDA Critical Path Initiative.
While experimental validation is warranted, the initial discovery and qualification time is considerably accelerated with a genomic approach. Genomics offers the ability for global assessment of expression levels of thousands of genes in parallel, within and across species, in both baseline and altered conditions, to better study specific toxicities and disease indications.
The use of large gene expression databases enables a rapid in silico approach to the discovery and qualification of bridging biomarkers and associated tissue specificity.
James T. MacGregor, of the Food and Drug Administration National Center for Toxicological Research, and Bernard A. Schwetz, of the Department of Health and Human Services, presented at an NIEHS Metabolic Profiling forum in May 2003.
They cited the major limitation of non-clinical toxicological practice as the uncertainty of quantitative extrapolation from laboratory models to the human. Genome-based analyses can often determine if there is a species-specific difference in response by examining thousands of potential markers simultaneously, thus building a more detailed biological picture. These results provide the context to designing more definitive studies, before tremendous amount of money has been spent: studies that provide a more quantitative extrapolation.
MacGregor and Schwetz also identified the primary opportunity as the identification of bridging biomarkers that permit monitoring of functional pathways, damage and damage-response in humans and laboratory models.
However, as echoed by William Stokes, from NIEHS/NICEATM, in a public forum at the ISRTP Workshop in November 2005, moving alternative methods, such as a multi-faceted bridging biomarkers approach, out of the lab and towards validated use and implementation is not without its challenges.
Stokes cited five barriers, three of which were related to regulatory needs and requirements. The other two were:
These challenges are at first glance overwhelming, and may have contributed to the slow progress in the field of biomarker discovery.
With applications that span discovery, development and healthcare, what drive an effort focused on discovering bridging biomarkers and who will lead it? Gene Logic has the biological samples, toxicogenomics and human genomic databases, as well as expertise in data analysis and interpretation, to help accelerate the industry's approach to innovating biomarker discovery.
Gene Logic's vast repositories of data and samples allow it to customise a programme specific to any question.
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Scientists worldwide know Gene Logic for compiling the largest and most detailed proprietary knowledgebase of gene expression profiles of human and animal tissues and cells. This expertise, combined with its industry-leading informatics capabilities is the foundation for Gene Logic's growing portfolio of innovative solutions that include gene expression and toxicogenomics databases, software tools, data generation, and professional services. These capabilities give it unique qualifications to help its clients make faster, better compound decisions.
Whether as an outsourcing partner for data generation, expert analysis and services or to enhance internal capabilities, Gene Logic offers solutions designed and scaled to meet technical and economic requirements, helping to saving time and money in the lengthy and costly drug development process. As a result of these partnerships, scientists are provided with answers to critical questions arising throughout the drug development process:
Successful implementation of biomarkers in drug development can accelerate development timelines, thus enabling earlier decision making and increasing the success of drug candidates in preclinical safety testing and clinical trials. Gene Logic systems enable the identification, prioritisation and confirmation of drug targets and biomarkers. The depth and breadth of gene expression data helps to identify the best biomarker candidates for target identification and drug development. Its analytical tools allow the selection of drug targets that display unique expression profiles with respect to human tissue type and disease indication. And, to help ensure success, Gene Logic scientists are available to provide in-depth, personal consultations.
Gene Logic can augment the understanding and prioritisation of drug candidates based on their potential for human toxicity from predictive and mechanistic analyses. The resulting wealth of information allows for better informed drug development decisions, advancing the most promising candidates.
In clinical development, genomics data is applied to aid in patient stratification, helping identify those patients who may be best suited for, and more responsive to, particular drugs and therapies.
The market is exerting tremendous pressure on developers to produce safer, more effective drugs. This, along with shrinking research and development budgets, places urgency on fine-tuning and accelerating activities throughout the drug discovery and development processes. Gene Logic's growing portfolio of innovative solutions includes gene expression and toxicogenomics databases, software tools, data generation, and professional services. It provides application support for:
With Genomics solutions, a Gene Logic partner has the ability to access the gene expression profiles of thousands of normal and diseased human and animal tissues in the key therapeutic areas of oncological, inflammatory, cardiovascular and central nervous system diseases, as well as metabolic disorders. Embedded in the genomics content is integrated biological pathway knowledge that provides a deeper understanding of the activity of cellular processes at the gene expression level. This knowledge allows one to adopt a systems biology approach to understanding disease mechanisms and to establish intellectual property.
Gene Logic's genomic solutions portfolio includes the BioExpress® database and disease-specific data suites for in-depth studies, the ASCENTA® and SCIANTIS™ systems for rapid, web-based gene expression analysis, and Microarray Data Generation and Analysis™ Services for quality results. Its toxicogenomics solutions include a variety of economical products and services that range from full ToxExpress® System subscriptions, ToxSuite™ data sets and web-based software solutions such as ToxShield™ Suites to professional services such as mechanism of toxicity reports and ToxScreen™ reports.
Gene Logic helps pharmaceutical and biotechnology companies as well as academic and government institutions accelerate drug development through a genomics and toxicogenomics solutions portfolio.