Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 7.61M | Year: 2014
The infectious diseases burden imposed by the parasites of Trypanosomatidae family represents a huge problem on peoples lives in countries where these diseases are endemic. Problems associated with existing drugs include inefficient delivery, insufficient efficacy, excessive toxicity and increasing resistance. New drugs are urgently needed now and in the foreseeable future. The New Medicine for Trypanosomatid Infections (NMTrypI) consortium uses a highly interdisciplinary approach to optimize pteridine, benzothiazole and miltefosine derivatives, as well as natural products against Trypanosomatids. The lead compounds target mechanisms that are associated with protozoa virulence and pathogenicity. The major objectives of this 3-year project are: i) development of drug leads which may be used in combination with a known or an investigational drugs, by using a common drug discovery platform established by experts in their respective fields, ii) development of pharmacodynamic biomarkers enabling the proteomic profiling of compound efficacy and early identification of drug resistance. NMTrypI addresses sleeping sickness, leishmaniasis, and Chagas disease. The partners are SMEs (5) and academics (8) in Europe and in disease-endemic countries (Italy, Greece, Portugal, Sudan, and Brazil). The new platform enables high throughput screening of compound libraries, lead development, testing in relevant animal models, as well as toxicology and safety testing. NMTrypI will translate drug leads into drug candidacy through 6 scientific work packages (WPs1-6) supported by two transversal WPs dedicated to project dissemination and management. The major strength of the consortium lies in the complementary partnersexpertise and the integrated platform that will provide: - at least 1-2 innovative, less toxic and safer drug candidates for Trypanosomatid infections compared to existing ones, - early phase biomarkers for efficacy prediction (overall improved efficacy and safety)
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 7.80M | Year: 2014
This project aims to unite global efforts to target the highly druggable class of enzymes called cyclic nucleotide phosphodiesterases (PDEs) in the fight for neglected parasitic diseases (NPD). It will establish a drug discovery platform, PDE4NPD, that combines phenotypic screening with efficient target-centric drug discovery, including target validation, various strategies for compound screening, PDE hit and lead optimization, safety and toxicology assessments and evaluation of anti-parasitic activity. The platform will make use of the target class expertise that the participating SMEs have gained when developing drugs for human and parasite PDEs, while all public partners offer proven experience in the field of NPD. The SMEs will adopt and progress existing PDE inhibitors that are in different stages of the drug discovery pipeline (i.e., target validation, hit and lead optimization). The current portfolio of inhibitors have clinical potential for treating sleeping sickness, Chagas disease and leishmaniasis. Finding novel hits and leads for the PDEs that are associated with helminth diseases is also foreseen. The platform is open for targeting other NPD, and a broad panel of phenotypic screens (including malaria) is available to test PDE inhibitors. The phenotypic screening is performed by world-renowned groups, including two institutes in endemic countries. By capturing human and parasite PDE-related data in annotated chemogenomics databases, PDE-4-NPD will achieve the knowledge accumulation that is typical for target-centric approaches, thereby making the NPD drug development more efficient and enabling the SMEs to take advantage of the molecular understanding that is key for developing new medicines. The PDE4NPD platform constitutes an ideal basis for creating fruitful collaborations with both public and private partners word-wide.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.0-1 | Award Amount: 5.23M | Year: 2014
Cell-based screenings are today a necessary tool for all types of clinical development and/or market approval of new drugs and chemicals. The major change in the last decade is a shift towards more physiologically relevant yet complex and sensitive cell models, like stem cells, and more recently, the shift to human induced pluripotent cells. Stem-cell technology has the potential to revolutionize drug discovery, making models available for primary screens, secondary pharmacology, safety pharmacology, metabolic profiling and toxicity evaluation. The overall aim of DropTech is the development of automated handling processes for stem cells with integrated readout methods, required for the use of stem cells in high-throughput assays such as the embryonic stem cell test (EST). DropTech will result on the one hand in a fully automated screening platform, usable by the industrial partners for reproducible and standardized high-throughput screening services and aggregate production. On the other hand a system that is directly exploitable for industrialization and marketing will be available to perform reliable and fast at least semi-automated screening approaches for customers. Therefore, the complete workflow of the EST, including stem cell expansion, embryoid body formation in hanging drops and transfer to 2D conditions will be automated using robotic and microfluidics systems. This will enable standardized, fast and efficient embryotoxicity screenings reducing the need for animal tests. DropTech will enable testing in a small- and medium-scaled budget accessible for SMEs and academia in the field of biotech and biomedicine. The DropTech platform will have therefore a significant impact on the development of new medication and therapies and will enable personalized medicine approaches as well as - in future - regenerative medicine. DropTech facilitate the use of cell models with highest biological relevance (human pluripotent stem cells) in their native conformation.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-1 | Award Amount: 7.88M | Year: 2013
Atherosclerosis and its most disabling sequelae, coronary artery disease (CAD) and stroke, are leading causes of death in Europe. Until now, preventive and therapeutic interventions for these diseases aim at ameliorating the effects of established cardiovascular risk factors. More recently, results of genome-wide association (GWA) studies added to our perception of mechanisms leading to atherosclerosis. At present, over 40 CAD and several genomic risk loci have been identified, the majority through efforts led by the applicants. Some genes at these loci work through known risk factors such as lipids and, in fact, are already established or evolving treatment targets. However, this is not true for the majority of risk variants, which implies that key pathways leading to atherosclerosis are yet to be exploited for therapeutic intervention. This EU network (CVgenes@target), which brings together an equal number of SME- and academic partners, will utilize genomic variants affecting atherosclerosis risk for identification of both underlying genes and affected pathways in order to identify, characterize, and validate novel therapeutically relevant targets for prevention and treatment of CAD and stroke. In programme 1 we will investigate molecular mechanisms at the genomic loci in order to further unravel causal genes, in programme 2 we will explore in vitro and in vivo whether the pathways disturbed by causal genes are suitable for therapeutic intervention, and in programme 3 we will establish assays and initiate high throughput screens to tackle therapeutically attractive targets. Our resources including large OMICs and state-of-the-art bioinformatics platforms as well as multiple, already established in vitro and in vivo models support the feasibility of the approach. In fact, two genomic risk loci (ADAMTS7 (CAD); HDAC9 (stroke and CAD)), both identified in GWA studies under direction of the applicants, already revealed attractive targets for therapeutic intervention.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.3-3 | Award Amount: 7.70M | Year: 2011
Modern lifestyle has dramatically changed the daily rhythms of life. Physical activity, diet and light exposure are no longer restricted to daytime hours, as technical and economical de-mands fuel the necessity to work outside usual working hours. Recent studies show that al-tered light exposure, shifted exercise patterns and untimely food intake following extended active periods into the night disturb the circadian clocks and severely disrupt endocrine and metabolic processes, contributing to an increased risk of type 2 diabetes/obesity. Especially shift workers constituting 20% of the European working population are affected by this prob-lem. Until now only few studies investigating circadian rhythm disturbances in the context of type 2 diabetes/obesity have been conducted in man. Within EuRhythDia a consortium of leading scientists supported by research-intensive SMEs aims to close this gap. The objective of the project is to achieve breakthroughs in the understanding of the causality between inner clock rhythm disturbances and the development of type 2 diabetes/obesity, and to verify whether re-setting the circadian clock through lifestyle interventions (exercise, diet, light exposure and melatonin intake) alters cardiometabolic risk to a clinically relevant degree. The project is based on shift workers as a model and combines genetic, epigenetic, proteomic, metabolomic, physiological, and clinical approaches. The consortium has direct access to well characterised human data incl. individuals predisposed to type 2 diabetes via LUPS co-hort. Additional small interventional and validation cohorts of shift workers and high risk juveniles will be recruited, and supportive animal studies will be conducted. Through the de-velopment of novel diagnostic assays enabling identification of patients at risk and elaboration of targeted prevention guidelines focusing on shift workers and juveniles, EuRhythDia will contribute to a positive impact on European citizens` health.