Biomarkers Assessment in Neurotoxicity Symposium
Download Biomarkers Assessment Neurotoxicity Brochure
About This Conference:
Cambridge Healthtech Institute’s inaugural symposium on Biomarker Assessments in Neurotoxicity will cover conventional neurotoxicity testing based on gross morphological and histopathological endpoints and neurotoxicity assays that detect molecular markers of neural damage. The talks will also highlight some of the novel fluid-based markers, protein biomarkers, neurobehavioral assays, in vivo imaging tools, being developed for accurate prediction of neurotoxicity. The speakers will participate in a panel discussion to address specific concerns and questions that the attendees may pose.
|
Monday, June 4
8:00-8:55 am Registration & Morning Coffee
8:55 Chairperson’s Remarks
Andreas Jeromin, Ph.D., Banyan Biomarkers, Inc.
9:00 Current Biomarkers of Neurotoxicity: Conventional Morphological Analyses
Brad Bolon, D.V.M., Ph.D., DACVP, DABT, Veterinary Pathologist, Veterinary Biosciences; Associate Professor, Clinical, The Ohio State University
Conventional neurotoxicity testing depends on morphological biomarkers to screen neural tissues for xenobiotic-related changes. Gross morphological endpoints are generally limited to the brain and include examination of structural landmarks and acquisition of total brain weight. Histopathological endpoints are limited to light microscopic evaluation of tissue sections. Neurotoxicity assays detect various molecular markers to show patterns indicative of a response to prior damage. Despite some limitations, routine morphological methods represent the current “gold standard” of testing and they will undoubtedly remain the benchmark against which potential novel biomarkers will be validated.
9:30 Novel Fluid-Based Biomarkers of Neurotoxicity
Andreas Jeromin, Ph.D., Director, Business Development and Analytical Service Lab, Banyan Biomarkers, Inc.
We have used a neuro-proteomics approach to identify biomarkers of brain injury and develop sensitive assays for CSF, plasma and serum. This panel of biomarkers includes UCH-L1, a member of the ubiquitin-proteasome pathway and marker of cell body injury, GFAP, a marker of gliosis, and nonerythoid alphaII-spectrin degradation products (SBDPs). SBDP-145 which monitors necrosis/neurodegeneration shows promise as novel translational safety biomarker and we propose these biomarkers be part of nomination initiative for biomarkers in neurotoxicity.
10:00 GFAP and Related Glial Proteins as Biomarkers of Neurotoxicity
James O’Callaghan, Ph.D., Head, Molecular Neurotoxicology Laboratory, Health Effects Laboratory Division, CDC-NIOSH
Development and implementation of gliosis (glial reaction to nervous system damage) biomarkers represents a broadly applicable approach for neurotoxicity safety assessment. Using a panel of known neurotoxic agents we have shown the astroglial protein, GFAP, to be a sensitive and specific indicator of the neurotoxic condition. The implementation of GFAP and related glial biomarkers in neurotoxicity screens may serve as molecular signatures predictive of adverse effects on the nervous system.
10:30 Coffee Break
10:45 Comparative Results of Intrathecal LPS Exposure in the Spinal Cord of Rats Using Three Biomarker Techniques (Cytokines, PET and IHC)
Ingrid D. Pardo, D.V.M., M.S., DipACVP, Senior Principal Scientist and Neuroanatomist, Toxicologic Pathology, Pfizer, Inc.
Rats were exposed to intrathecal LPS with the purpose to validate a model of CNS inflammation/pain using PET as biomarker. Microglia cell activation at different time points after LPS injection was evaluated by cytokines and IHC analyses in serum/CSF and tissue, respectively. PET imaging was performed to assess binding of tracer to activated microglia. IL-1β in CSF was found to be the most sensitive biomarker of microglia cells activation at 24 hours post LPS injection.
11:15 CNS/Neurobehavioral Safety Biomarkers in Pre-Clinical Drug Research
James Lynch, Ph.D., Senior Scientist III, Integrative Pharmacology, Global Pharmaceutical Research and Development, Abbott Laboratories
Potential CNS/neurobehavioral side effects should be uncovered as soon as possible during the drug discovery and development process to help determine whether to shift resources to other compounds. Balancing this with the relatively limited finances and head count available during the earlier stages of pre-clinical drug research, this session discusses which CNS/ neurobehavioral safety pharmacology assays produce the most critical data in regards to further drug development, and optimization of such assays.
11:45 Translational Studies of TSPO as a Biomarker of Neurotoxicity
Tomas Guilarte, Ph.D., Leon Hess Professor & Chairman, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University
12:15 pm Enjoy Lunch on Your Own
2:00 Functional Assessment of Neurotoxicity: Cognitive Dysfunction in Animal Models and its Relevance to Humans
Merle G. Paule, Ph.D., Fellow, A.T.S., Director, Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration
A variety of behavioral instruments are available for assessing important aspects of cognition in both animals and humans and, in many cases, the same instruments can be used in both. As data accumulate, we continue to see that our attempts to adapt animal-appropriate tasks for the study of important aspects of human cognition—and their disruption by chemicals—are proving to be very fruitful.
2:30 Pre-Clinical in vivo Imaging of Neurotoxicity
Serguei Liachenko, Ph.D., Director, Bio-Imaging, National Center for Toxicological Research, Food and Drug Administration
Modern in vivo imaging technologies like magnetic resonance imaging and spectroscopy have attained an important role in medical research due to low invasiveness and ability to provide functional information about biological systems. Such information could be obtained from the same subject repeatedly and with the least possible interference, which makes in vivo imaging a unique and indispensable tool to support drug safety evaluation and other toxicological research in pre-clinical settings.
3:00 Using Pre-Clinical fMRI to “Finger Print” Drugs with Black Box Warnings for Suicide
Craig Ferris, Ph.D., Professor, Pharmaceutical Sciences, School of Pharmacy, Director, Ctr for Translational Imaging, Northeastern University
There are no pre-clinical behavioral or biochemical tests that can screen for a drug’s adverse effect on risk for suicide or self-harm. Pharmacological magnetic resonance imaging (phMRI) in awake rats is used to identify the integrated neural network(s) activated by drugs. Activation patterns for different classes of approved drugs with black box warnings as having risk for suicide were “finger printed” using BOLD imaging. The common neural network or the fMRI “finger print” of drugs for risk of suicide contains many of the same brain areas associated with schizophrenia.
3:30 Refreshment Break
4:00 Interpretations and Predictions from Neurobehavioral Evaluations in Rodents
Virginia C. Moser, Ph.D., D.A.B.T., Toxicity Assessment Division, U.S. Environmental Protection Agency
Neurobehavioral evaluations are routine components for neurotoxicity testing of pharmaceutical and environmental chemicals. Use of standardized protocols can provide a database describing profiles of effect for a variety of chemicals and neurotoxic mechanisms. Integration of these tests with complementary evaluations of the structure and function of the nervous system is necessary for accurate predictions of neurotoxicity.
4:30 PANEL DISCUSSION
5:15 End of Symposium
Download Biomarkers Assessment Neurotoxicity Brochure