Das Projekt "Profiling the toxicity of new drugs: a non animal-based approach integrating toxicodynamics and biokinetics (PREDICT-IV)" wird vom Umweltbundesamt gefördert und von Universität Würzburg, Institut für Pharmakologie und Toxikologie, Lehrstuhl für Toxikologie durchgeführt. The overall aim of Predict-IV is to develop strategies to improve the assessment of drug safety in the early stage of development and late discovery phase, by an intelligent combination of non animal-based test systems, cell biology, mechanistic toxicology and in-silico modelling, in a rapid and cost effective manner. A better prediction of the safety of an investigational compound in early development will be delivered. Margins-of-safety will be deduced and the data generated by the proposed approach may also identify early biomarkers of human toxicity for pharmaceuticals. The results obtained in Predict-IV will enable pharmaceutical companies to create a tailored testing strategy for early drug safety. The project will integrate new developments to improve and optimize cell culture models for toxicity testing and to characterize the dynamics and kinetics of cellular responses to toxic effects in vitro. The target organs most frequently affected by drug toxicity will be taken into account, namely liver and kidney. Moreover, predictive models for neurotoxicty are scarce and will be developed. For each target organ the most appropriate cell model will be used. The approach will be evaluated using a panel of drugs with well described toxicities and kinetics in animals and partly also in humans.
Das Projekt "Embryonic stem cell-based novel alternative testing strategies (ESNATS)" wird vom Umweltbundesamt gefördert und von Universität Köln, Klinikum, GB1, DFS-Verwaltung durchgeführt. ESNATS aims at developing a novel toxicity test platform based on embryonic stem cells (ESC), especially human ESC (hESC), to accelerate drug development, reduce R&D costs and propose a powerful alternative to animal tests (3 Rs). ESNATS will address current drug-testing shortcomings: - testing takes place late in the development cycle - animal test systems bear the risk of non-prediction due to inter-species variation - non-ESC assays rely on primary cells or cells of malignant origin that are hard-to-standardise and limited in regard to quantity, homogeneity and genetic diversity - existing assay systems based on primary animal cell lines do not reliably represent the physiological situation ESNATS will develop a battery of toxicity tests using hESC lines subjected to different standardised culture protocols. Tests will cover embryoid bodies in different developmental stages and differentiated derivatives including gamete and neuronal lineages, complemented with test systems for hepatic metabolism. Predictive toxicogenomics and proteomics markers will be identified. The individual tests will be integrated into an 'all-in-one' test system. To enable future industrial use ESNATS will prepare automating and scaling up of hESC culture. The predictivity, quality and reproducibility of ESNATS will be evaluated.
Das Projekt "Monoclonal antibody-targeted carbon nanobues against cancer (ANTICARB)" wird vom Umweltbundesamt gefördert und von University College London durchgeführt. Objective: ANTICARB attempts to exploit the advantages offered by a novel nanotechnology platform carbon nanotubes and apply them to a clinically established therapeutic modality targeted antibody therapy for the creation of hybrid nanotechnology-based monoclonal antibody targeted cancer therapeutics. ANTICARB combines two emerging technologies, antibody and nanotube technology, in a way that will allow safe development of antibody-nanotube conjugates and explore their swift translation into a clinical oncology setting. By combining proven, clinically used, anti-cancer agents' antibodies with a novel nanotechnology-based platform made of advanced nanomaterials, ANTICARB aims at enhancing the therapeutic potency of the antibody and establish a new paradigm for oncology therapeutics. The ability of carbon nanotube technology to transport antibodies into the tumour cell cytoplasm may lead to validation of specific intracellular targets for oncology. This objective will be reached by adopting a multidisciplinary approach and by bringing together expertise from the fields of drug delivery, molecular biology, chemistry, engineering, pharmacology and toxicology.