Automated Tyrosine Kinase Inhibitor Cardiotoxicity Assay in Zebrafish
Poster May 03, 2012
Olaia Holgado, Juan Maria Virto, Isaskun Ibarbia, Patrice Dubreuil, Didier Pez, Ainhoa Letamendia, Martine Humbert, Alain Moussy, Carles Callol-Massot
The zebrafish embryos have recently gained relevance in biomedical research thanks to some of its characteristics including embryo transparency, small size, ease of manipulation and possibility to evaluate different internal organs avoiding invasive methodologies. Combined with the possibility to adapt the model with an automatic device and the reduced cost associated to each assay, the model is an ideal killer experiment in early phases of drug discovery as well as a novel method to increase the selection arguments to reduce the candidates to enter into the Drug Development process.
Cardiotoxicity is one of the most important reasons for drug attrition during the process of Drug Development. Evaluation of cardiotoxicity and especially HERG channel inhibition is described in regulatory guidelines, but limitations demands the development of new complimentary assays that can also evaluate the heart function from a histolic point of view. Biobide has set up a novel in vivo automated platform that allows testing compounds in zebrafish embryos.
To evaluate and validate the quality of the analysis system, the model and the value of the information, we have used a panel of blind-coded Tyrosine kinase inhibitors that had been previously described in other in vitro and in vivo assays. The results indicate that our automated method provides with high informative and complementary data that can significantly improve the process of selection of new candidates with low or no cardiotoxicity.
Despite the developments in conventional PCR, the complexity of multiplex Real Time PCR is still limited due to the lack of sufficient detection channels. To achieve high-end multiplexing capacity on standard Real Time PCR machines, Anapa Biotech has developed the MeltPlex® technology (see box on right).READ MORE
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.