SOT 2016: Chewing on Hard Science in the Big Easy. The first of a four-part series.
The concept of biomarkers isn’t really new. Historical evidence suggests that ancient Egyptians measured the pulse to monitor disease and that uroscopy as a science began in the days of Hippocrates.
But an explosion in new genomic technologies over the past decade have given biomarkers—a term that only came into vogue several decades ago—a new twist and a much wider audience, noted William Mattes, the US Food and Drug Administration’s Director of Systems Biology, in his 2013 book, “The Path from Biomarker Discovery to Regulatory Qualification.”
There are now hundreds, if not thousands, of biomarkers validated or in development. As proof of the growing use and relevance of biomarkers in drug development, the US Food and Drug Administration (FDA)’s 2013 Guidance for Industry on Bioanalytical Method Validation (BMV) included, for the first time, a section on biomarkers to help address some of the many questions about the accuracy and reliability of biomarker data, particularly with respect to clinical studies.
And biomarkers continue to be a popular draw at science meetings like the Society of Toxicology’s annual five-day conference kicking off in New Orleans on Sunday. Different categories and applications of biomarkers will be a theme of three separate poster sessions, and the subject of a special lecture. It will also be the focus of an exhibitor’s session on Monday chaired by Simon Lavaleé, Scientific Director, Biomarkers at CRL’s Safety Assessment site in Montreal, who specializes in the development and validation of biomarker immunoassays and Rebecca Young, a research scientist based at our Safety Assessment site in Reno, and an expert in biomarker development for pre-clinical and clinical studies.
In the field of toxicology, biomarkers have been classified as markers of exposure, effect and susceptibility, but developing and validating highly-sensitive methods to measure biomarkers and understanding what the data really says is complicated. Eureka blogged about some of these challenges in a recent Q&A with Lavaleé and his colleague from our Reno site, Kelly Colletti. At SOT, Lavaleé and Young’s session will focus on how our increased reliance on biomarkers to evaluate the toxicity and/or efficacy of new drugs during preclinical toxicology studies has driven routine validation of new analysis methods. The session will also look at why some of the commercial kits may need to be amended in order to suit regulatory compliance.
Eureka will also follow another Charles River exhibitor’s session that broadens the ongoing dialogue surrounding methods of detecting life-threatening cardiac arrhythmias in drug compounds. Eureka has written extensively about the Comprehensive in vitro Proarrhythmia Assay (CiPA) Initiative, which is transforming how we test drugs for cardiac toxicities, and as its title suggests shifts the focus away, somewhat, from in vivo testing. (You can find some of our posts about this paradigm shift here, here and here.) Still, Charles River Safety Pharmacologist Robert Kaiser says the fate of the clinical Thorough QT (TQT) study that developers have historically had to complete in order for their drug to get to market remains a topic of great interest. Kaiser has helped organize a Tuesday afternoon session at SOT that focuses on the future of risk assessment studies in animals given the recent regulatory changes occurring at the FDA, including the future roll-out of CiPA.
The session will present results of a case study of Ouabain, a drug given in low doses to treat hypotension, but was chosen for this study for its pro-arrhythmic properties. The data to be presented have implications on the context of in vitro testing and the predictivity/translatability of those results in vivo. “With so much current emphasis on CiPA, in vivo studies are as important as ever,” says Kaiser.
Building hearts, avoiding Zika
We’ll also be checking out one of the opening plenaries by Doris Taylor of the Texas Heart Institute in Dallas, who will be talking about building a heart from scratch—from cells to tissues to organs. With heart disease the leading cause of death in much of the world, and few treatments to overcome it, the ability to regenerate a heart and eliminating the dysfunctional elements in the process would be an amazing achievement.
Some of the most interesting discussions at meetings occur at poster presentations, where it is actually possible to have one-on-one conversations with scientists if you can manage to find your way through the maze of abstracts. This year Charles River is presenting or is listed as an author on 18 poster presentations, and our scientists are chairing two poster sessions, one about ocular toxicology and the other on methods and measurements of animal models.
One topic that hasn’t popped up in the program, but which we suspect will be mentioned during some discussions, is the mosquito-borne Zika virus. (We are, after all, meeting in the sub-tropics). Alan Hoberman, a reproductive toxicologist at Charles River’s Safety and Assessment site in Horsham, Pa., and the incoming president of the Teratology Society, said the safety of preventive vaccine candidates or effective treatments for Zika are probably the topics of most interest to toxicologists. “But those are still in the research stage,” he said. “It is very early days.” So he says most of the dialogue will likely be of the water-coolor variety. Hoberman says a special report about the virus will be on the agenda of the Teratology Society’s upcoming meeting in June, where we’ll likely learn more about how the research is progressing.
Eureka will be blogging live at SOT. We hope you check out our posts and leave a comment or two. You can also read more about what Charles River will be doing at SOT by logging on here.
See you in the Big Easy!
How to cite:
McEnery, Regina. Toxicologists Unite!. Eureka blog. Mar 10, 2016. Available: https://eureka.criver.com/toxicologists-unite/