March 19, 2017 by Owen Green & Louise Youngs
In the Keynote MRC lecture, Paul Elliott (Imperial College, UK) discussed ‘the exposome: challenges and opportunities’. Blood pressure was identified as the leading cause of morbidity and mortality, and the presentation outlined the importance of the metabolome, gut microbiome and nutriome in driving the epidemiological transmission to chronic non-communicable diseases. Elliott suggested that elucidating metabonetworks, via both targeted and genome-wide association studies (GWAS) of national cohorts (i.e. BIOBANK) may enable precision medicine to offset genetic risk through lifestyle intervention.
In the workshop on ‘Challenges and novel approaches evaluating developmental and reproductive toxicity of biotherapeutics’ the regulatory context (ICH S5, ICH S6 and ICH S9) and complexities of DART studies for biologics were outlined. In an overview by the chair, the need to consider the target pathway and its relative importance in pregnancy and development was stressed. In a discussion of alternative embryo-foetal toxicity assessments of anti-cancer biopharmaceuticals, LaRonda Morford (Eli Lilly, US) discussed the approach for Cyranza (Ramucirumab) and Lartruvo (Olaratumab). The session followed with a discussion of biopharmaceuticals blocking the PD-1/PD-L1 pathway, oligonucleotide based therapies and the US EPA’s perspective to evaluation.
In the afternoon, Louise and Owen attended the Symposium on ‘Novel in vitro and in silico platforms for modelling developmental and reproductive toxicity’ chaired by Thomas Knudson (US EPA, US). Detailing an innovative study networking in vitro co-cultures, Shuo Xiao (University of South Carolina, US) outlined a microphysiological model of the female reproductive tract. The microfluidic platform recapitulates the human 28-day menstrual cycle, mimicking morphological changes in the follicles and corpus luteum formation in vivo. The author suggested that the system could be used to introduce sexual dimorphism of tissues (i.e. liver). In light of the vast number of substances to be evaluated under the EDSP Tier 1, Nicole Kleinstreuer (NIEHS, US) discussed the need for pathway based models to predict development and reproductive toxicities, such as the recently coined EDSP21. The high-throughput method accurately predicted Uterotrophic assay results and a new Integrated Chemical Environment (ICE) information hub was released http://ice.ntp.niehs.nih.gov/. In an insightful presentation, Randolph Ashton (University of Wisconsin, US) outlined the use of human pluripotent stem cells (hPSC) to model organotypic brain cell phenotype diversity and tissue cytoarchitecture. To close the session, Thomas Knudsen (US EPA, US) and George Daston (Procter & Gamble, US) discussed the combination of cheminformatics and non-animal methods for developmental and reproductive toxicity.