Biomarkers: the next step
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?
Can genomics help?
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.
Overwhelming challenges
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:
- Insufficient availability of animal and human reference data
- Lack of quantitative objective mechanistic and early biomarker data from animal and human studies to assist in modelling toxic mechanistic processes across animal models to humans
These challenges are at first glance overwhelming, and may have contributed to the slow progress in the field of biomarker discovery.
Towards a solution
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.
For more information, contact Loralyn Mears, PhD, at lmears@genelogic.com.
< Back to Drug Discovery index
< Back to Market Resources index
