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.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE.2010.3.2-01 | Award Amount: 3.85M | Year: 2011
The aim of MARINE FUNGI is the demonstration of sustainable exploitation of marine natural resources providing appropriate culture conditions for the underutilised group of marine fungi, thus enabling efficient production of marine natural products in the laboratory and also in large scale cultures, avoiding harm to the natural environment. The focus of MARINE FUNGI are new anti-cancer compounds The project will carry out the characterisation of these compounds to the stage of in vivo proof of concept ready to enter further drug development in order to valorise the results of the project. MARINE FUNGI covers two approaches to gain effective producer strains: a) Candidate strains originating from one partners strain collection will be characterised and optimised using molecular methods. b) New fungi will be isolated from unique habitats, i.e. tropical coral reefs, endemic macroalgae and sponges from the Mediterranean. Culture conditions for these new isolates will be optimised for the production of new anti-cancer metabolites. MARINE FUNGI will develop a process concept for these compounds providing the technological basis for a sustainable use of marine microbial products as result of Blue Biotech. The project will explore the potential of marine fungi as excellent sources for useful new natural compounds. This will be accomplished by the formation of a new strongly interacting research network comprising the scientific and technological actors, including 3 SMEs and 2 ICPC partners, necessary to move along the added-value chain from the marine habitat to the drug candidate and process concept. The generated and existing knowledge will be disseminated widely for the valorisation of the project results.
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.2013.2.4.2-1 | 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.
Bushman J.,New Jersey Center for Biomaterials |
Mishra B.,University of Hamburg |
Ezra M.,New Jersey Center for Biomaterials |
Gul S.,European ScreeningPort GmbH |
And 8 more authors.
Neuropharmacology | Year: 2014
Glycans attached to the cell surface via proteins or lipids or exposed in the extracellular matrix affect many cellular processes, including neuritogenesis, cell survival and migration, as well as synaptic activity and plasticity. These functions make glycans attractive molecules for stimulating repair of the injured nervous system. Yet, glycans are often difficult to synthesize or isolate and have the disadvantage to be unstable in a complex tissue environment. To circumvent these issues, we have screened a library of small organic compounds to search for structural and functional mimetics of the neurostimulatory glycan polysialic acid (PSA) and identified the 5-HT 4 receptor agonist tegaserod as a PSA mimetic. The PSA mimicking activity of tegaserod was shown in cultures of central and peripheral nervous system cells of the mouse and found to be independent of its described function as a serotonin (5-HT4) receptor agonist. In an in vivo model for peripheral nerve regeneration, mice receiving tegaserod at the site of injury showed enhanced recovery compared to control mice receiving vehicle control as evidenced by functional measurements and histology. These data indicate that tegaserod could be repurposed for treatment of nervous system injuries and underscores the potential of using small molecules as mimetics of neurostimulatory glycans. © 2013 Elsevier Inc. All rights reserved.
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: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.30M | Year: 2013
Multidrug resistant bacteria are now ubiquitous in both hospitals and the larger community. Drug-resistant pathogens are becoming increasingly pervasive, for example, the resurrection of tuberculosis provides one ominous example highlighting the risk associated with evolved drug resistance. Moreover, many pharmaceutical companies abandoned this field and no truly novel active antibacterial compounds are currently in clinical trials. Obviously we need new antibacterial molecules and maybe, novel strategies to develop antibiotics. The novel aspect here is to use state-in-the art techniques to quantify rate limiting steps of individual components involved antibiotic penetration and to validate them at the cellular level. Such a system biology approach identifies bottlenecks of existing antibiotics and might suggest novel antibiotic therapy. In Gram-negative bacteria, where influx and efflux systems located in the Outer Membrane represent a physical bottleneck for any antibiotic to reach a potential target. The aim is to investigate the molecular and cellular mechanisms at the basis of the influx and efflux processes and to teach scientists with different scientific background to go beyond the classical faculty boarder. Bringing nanotechnology, physics, chemistry, computer modeling, pharmacology, microbiology together will facilitate the transfer of expertise acquired within the network in both academic and industry. To achieve these goals we propose a training program allowing young researcher to collaborate across traditional faculty boarder. Three partners from the private sector will actively participate, the first one is a SME developing unique nanodevices allowing high-throughput drug screening in the field of electrophysiology, the second one is engaged in developing novel antibiotics and the third one is working on drug screening and characterization. Moreover three global pharmaceutical companies will accept students for secondments.
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.
Brandl B.,University of Kiel |
Schneider S.A.,University of Kiel |
Loring J.F.,Scripps Research Institute |
Hardy J.,University College London |
And 2 more authors.
Movement Disorders | Year: 2015
The introduction of stem cell-associated molecular factors into human patient-derived cells allows for their reprogramming in the laboratory environment. As a result, human induced pluripotent stem cells (hiPSC) can now be reprogrammed epigenetically without disruption of their overall genomic integrity. For patients with neurodegenerative diseases characterized by progressive loss of functional neurons, the ability to reprogram any individual's cells and drive their differentiation toward susceptible neuronal subtypes holds great promise. Apart from applications in regenerative medicine and cell replacement-based therapy, hiPSCs are increasingly used in preclinical research for establishing disease models and screening for drug toxicities. The rapid developments in this field prompted us to review recent progress toward the applications of stem cell technologies for movement disorders. We introduce reprogramming strategies and explain the critical steps in the differentiation of hiPSCs to clinical relevant subtypes of cells in the context of movement disorders. We summarize and discuss recent discoveries in this field, which, based on the rapidly expanding basic science literature as well as upcoming trends in personalized medicine, will strongly influence the future therapeutic options available to practitioners working with patients suffering from such disorders. © 2014 International Parkinson and Movement Disorder Society.