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1.

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE

Mechanisms of recovery after severe spinal cord injury

  • 2 Million
  • Switzerland
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Mechanisms of recovery after severe spinal cord injury
Company Name ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Funded By 38
Country Switzerland , Western Europe
Project Value 2 Million
Project Detail

Severe spinal cord injury leads to a range of disabilities, including permanent motor impairments that seriously diminish the patients’ quality of life. In the framework of an ERC Starting Grant, my team and I developed a pragmatic therapy that restored supraspinal control of leg movement after complete paralysis in rats. However, the mechanisms underlying the effects of this intervention remain unknown. This fundamental knowledge is pivotal to operate a disruptive conversion from our empirical approach to an evidence-based strategy with clinical perspectives. Our therapy, termed neuroprosthetic rehabilitation, acts over two time windows. Immediately, electrical and chemical spinal cord stimulations mediate motor control of the paralysed hindlimbs. In the long term, will-powered training regimens enabled by electrochemical stimulation and robotic assistance promote neuroplasticity of residual connections—an extensive rewiring that reestablishes voluntary movement. Here, we propose to identify the circuit-level remodelling, computational principles, and molecular cues that govern the immediate and long-term recovery of motor functions. To address this knowledge gap, we will use our unique neuroprosthetic platform and next-generation experimental techniques for longitudinal assessment of neuroplasticity and function in freely behaving mice. These techniques combine optogenetics, circuit-level inactivation techniques, unconstrained chronic calcium imaging, virus-mediated tract-tracing and genetic manipulations. Our strategy consists of deploying a judicious association of these experimental techniques to establish causality between the reorganisation of the motor circuitry and functional recovery. This project will fertilize frontier research with new knowledge and ideas, ultimately accelerating clinical implementation of safer and more efficacious therapies to improve the quality of life for spinal cord injured individuals.

Sector Administration & Marketing

Contact Details

Company Name ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Address Batiment Ce 3316 Station 1 1015 Lausanne
Web Site https://cordis.europa.eu/project/rcn/203248/factsheet/en

2.

KATHOLIEKE UNIVERSITEIT LEUVEN

Validating C. elegans healthspan model for better understanding factors causing health and disease, to develop evidence based prevention, diagnostic, therapeutic and other strategies.

  • 7 Million
  • Belgium
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Validating C. elegans healthspan model for better understanding factors causing health and disease, to develop evidence based prevention, diagnostic, therapeutic and other strategies.
Company Name KATHOLIEKE UNIVERSITEIT LEUVEN
Funded By 38
Country Belgium , Western Europe
Project Value 7 Million
Project Detail

Healthspan (the life period when one is generally healthy and free from serious disease) depends on nature (genetic make-up) and nurture (environmental influences, from the earliest stages of development throughout life). Genetic studies increasingly reveal mutations and polymorphisms that may affect healthspan. Similarly, claims abound about lifestyle modifications or treatments improving healthspan. In both cases, rigorous testing is hampered by the long lifespan of model organisms like mice (let alone humans) and the difficulty of introducing genetic changes to examine the phenotype of the altered genome. We will develop C. elegans as a healthspan model. Already validated extensively as an ageing model, this organism can be readily modified genetically, and effects of environmental manipulations on healthspan can be measured in days or weeks. Once validated as a healthspan model, it can be used for an initial assessment of preventive and therapeutic measures for humans, as well as for risk identification and the initial evaluation of potential biomarkers. It will also prove useful to study interactions between genetic and various environmental factors.

Sector Administration & Marketing

Contact Details

Company Name KATHOLIEKE UNIVERSITEIT LEUVEN
Address Oude Markt 13 3000 Leuven
Web Site https://cordis.europa.eu/project/rcn/193245/factsheet/en

3.

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM

TRAF-STOP therapy to reduCe inflammation in athERosclerosis.

  • Plz Refer Document
  • Netherlands The
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TRAF-STOP therapy to reduCe inflammation in athERosclerosis.
Company Name ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Funded By 38
Country Netherlands The , Western Europe
Project Value Plz Refer Document
Project Detail

Atherosclerosis, the underlying cause of the majority of cardiovascular diseases, is a lipid driven, inflammatory disease of the large arteries. Despite a 25% relative risk reduction achieved by lipid-lowering treatment, the vast majority of atherosclerosis induced cardiovascular disease risk remains unaddressed. Therefore, characterizing mediators of the inflammatory aspect of atherosclerosis is a widely recognized scientific goal with great therapeutic implications. Blocking the co-stimulatory CD40L-CD40 dyad reduces atherosclerosis. However, long-term inhibition of CD40L or its receptor CD40 results in suppression of the immune system and poses a risk for thromboembolic events. Therefore, we focused on the downstream signaling pathways of CD40, and found that the interaction between CD40 and TNF-receptor-associated factor 6 (TRAF6) is the driving force for atherosclerosis. Using virtual ligand screening, we identified several small molecule inhibitors termed TRAF-STOPs that were modeled to bind to the CD40-binding domain of TRAF6. TRAF-STOPs significantly reduce (existing) atherosclerosis and treatment was well tolerated. The first toxicology results in mice show that there are no side effects. Here we pursue the hypothesis that TRAF-STOPs are excellent candidates to pass the translational pipeline towards a clinical application to treat atherosclerotic cardiovascular disease. Prof. Lutgens is one of the founders of the recently established start-up company Cartesio Therapeutics to be able to valorise our novel TRAF-STOPs. By the end of the PoC grant, we expect to have an oral drug available and to have completed toxicology and bio-distribution analysis in a large animal model (mini-pig) and have tested TRAF-STOPs in a pig model of atherosclerosis. This way, we hold a solid business case in our hands. The resulting business- and (pre-)clinical development plan and patent portfolio will then be ready for seed investment and venture capital funding.

Sector Administration & Marketing

Contact Details

Company Name ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Address Meibergdreef 15 1105az Amsterdam
Web Site https://cordis.europa.eu/project/rcn/224600/factsheet/en

4.

UNIVERSITY OF GLASGOW

Levitation with localised tactile and audio feedback for mid-air interactions

  • 3 Million
  • United Kingdom
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Levitation with localised tactile and audio feedback for mid-air interactions
Company Name UNIVERSITY OF GLASGOW
Funded By 38
Country United Kingdom , Western Europe
Project Value 3 Million
Project Detail

"This project will be the first to create, prototype and evaluate a radically new human-computer interaction paradigm that empowers the unadorned user to reach into levitating matter, see it, feel it, manipulate it and hear it. Our users can interact with the system in a walk-up-and-use manner without any user instrumentation. As we are moving away from keyboards and mice to touch and touchless interactions, ironically, the main limit is the lack of any physicality and co-located feedback. In this project, we propose a highly novel vision of bringing the physical interface to the user in mid-air. In our vision, the computer can control the existence, form, and appearance of complex levitating objects composed of ""levitating atoms"". Users can reach into the levitating matter, feel it, manipulate it, and hear how they deform it with all feedback originating from the levitating objects position in mid-air, as it would with objects in real life. This will completely change how people use technology as it will be the first time that they can interact with technology in the same way they would with real objects in their natural environment. We will draw on our understanding of acoustics to implement all of the components in a radically new approach. In particular, we will draw on ultrasound beam-forming and manipulation techniques to create acoustic forces that can levitate particles and to provide directional audio cues. By using a phased array of ultrasound transducers, the team will create levitating objects that can be individually controlled and at the same time create tactile feedback when the user manipulates these levitating objects. We will then demonstrate that the levitating atoms can each become sound sources through the use of parametric audio with our ultrasound array serving as the carrier of the audible sound. We will visually project onto the objects to create a rich multimodal display floating in space."

Sector Administration & Marketing

Contact Details

Company Name UNIVERSITY OF GLASGOW
Address University Avenue G12 8qq Glasgow
Web Site https://cordis.europa.eu/project/rcn/207474/factsheet/en

5.

ASSOCIATION POUR LA RECHERCHE ET LE DEVELOPPEMENT DES METHODES ET PROCESSUS INDUSTRIELS

Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicine

  • 2 Million
  • France
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Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicine
Company Name ASSOCIATION POUR LA RECHERCHE ET LE DEVELOPPEMENT DES METHODES ET PROCESSUS INDUSTRIELS
Funded By 38
Country France , Western Europe
Project Value 2 Million
Project Detail

Rupture of Aortic Aneurysms (AA), which kills more than 30 000 persons every year in Europe and the USA, is a complex phenomenon that occurs when the wall stress exceeds the local strength of the aorta due to degraded properties of the tissue. The state of the art in AA biomechanics and mechanobiology reveals that major scientific challenges still have to be addressed to permit patient-specific computational predictions of AA rupture and enable localized repair of the structure with targeted pharmacologic treatment. A first challenge relates to ensuring an objective prediction of localized mechanisms preceding rupture. A second challenge relates to modelling the patient-specific evolutions of material properties leading to the localized mechanisms preceding rupture. Addressing these challenges is the aim of the BIOLOCHANICS proposal. We will take into account internal length-scales controlling localization mechanisms preceding AA rupture by implementing an enriched, also named nonlocal, continuum damage theory in the computational models of AA biomechanics and mechanobiology. We will also develop very advanced experiments, based on full-field optical measurements, aimed at characterizing localization mechanisms occurring in aortic tissues and at identifying local distributions of material properties at different stages of AA progression. A first in vivo application will be performed on genetic and pharmacological models of mice and rat AA. Eventually, a retrospective clinical study involving more than 100 patients at the Saint-Etienne University hospital will permit calibrating estimations of AA rupture risk thanks to our novel approaches and infuse them into future clinical practice. Through the achievements of BIOLOCHANICS, nonlocal mechanics will be possibly extended to other soft tissues for applications in orthopaedics, oncology, sport biomechanics, interventional surgery, human safety, cell biology, etc.

Sector Administration & Marketing

Contact Details

Company Name ASSOCIATION POUR LA RECHERCHE ET LE DEVELOPPEMENT DES METHODES ET PROCESSUS INDUSTRIELS
Address Boulevard Saint Michel 60 75272 Paris
Web Site https://cordis.europa.eu/project/rcn/194483/factsheet/en

6.

UNIVERSITAET BERN

Synthetic viability of homologous recombination-deficient cancers

  • 2 Million
  • Switzerland
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Synthetic viability of homologous recombination-deficient cancers
Company Name UNIVERSITAET BERN
Funded By 38
Country Switzerland , Western Europe
Project Value 2 Million
Project Detail

Although various effective anti-cancer drug treatments have become available over the last decades, drug resistance remains the major cause of death of cancer patients. Striking examples are patients with tumors that are defective in DNA repair by homologous recombination (HR). Despite initial responses to cancer therapy, resistance of primary or disseminated tumors eventually emerges, which minimizes therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are often poorly understood. In the SYNVIA project I will address the problem of therapy escape by using powerful genetically engineered mouse models for BRCA1- and BRCA2-deficient breast cancer, which closely mimic the human disease. Due to the BRCA inactivation, the tumors that arise lack HR-directed DNA repair. Similar to the situation in cancer patients, we observe that cancer cells in these models eventually escape the deadly effects of chemotherapy or novel targeted drugs. Thus, these resistance models provide a unique opportunity to explore therapy escape mechanisms. I propose an approach that will take the in vivo analysis of therapy resistance mechanisms to a new level. By synergizing the advantages of next generation sequencing with functional genetic screens in tractable model systems, I will explore novel mechanisms that cause resistance of HR-deficient cancers by the loss of another gene (“synthetic viability”). I provide evidence that new mechanisms of resistance can be identified with this approach. In an innovative step, I will generate genome-wide alterations using the revolutionizing CRISPR/Cas technology. Mutations will also be introduced into 3D tumor organoid cultures, as we found that these are more physiologically relevant. I am convinced that the combination of these state-of-the-art approaches will yield highly useful information for designing effective approaches to circumvent or reverse therapy escape in human cancer patients.

Sector Administration & Marketing

Contact Details

Company Name UNIVERSITAET BERN
Address Hochschulstrasse 6 3012 Bern
Web Site https://cordis.europa.eu/project/rcn/202583/factsheet/en

7.

PERCUROS BV

Image-Guided Surgery (IGS) and Personalised Postoperative Immunotherapy To Improving Cancer Outcome

  • 4 Million
  • Netherlands The
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Image-Guided Surgery (IGS) and Personalised Postoperative Immunotherapy To Improving Cancer Outcome
Company Name PERCUROS BV
Funded By 38
Country Netherlands The , Western Europe
Project Value 4 Million
Project Detail

The basic concept of our proposal is to develop nanoparticle-based encapsulated libraries of different immunotherapeutic biomolecules for treatment after surgery as part of a novel cancer management strategy. The current state-of-art for the management of cancer starts with surgery, after identification of an accessible tumour mass. Surgery remains an effective treatment option for many types of cancer today and it is considered curative treatment for most solid tumours. It forms part of a multidisciplinary approach used in conjunction with radiotherapy or chemotherapy. These approaches, however, have several limitations, including inability of surgical resection to affect distal metastatic disease, toxicity to healthy tissues with chemotherapy and lack of effectiveness of radiation therapy in more aggressive tumours. The observation that cancer can relapse months or years after initial surgery implies that micrometastases still resides within the body in a latent state. Our proposal is to take cancer therapy to beyond state-of-art by implementing techniques which will take us into new directions. This includes a) new methods to identify immune gene profiles and biomarkers b) transgenic mouse models where the complex interactions that underlie immune function can be visualised as multiplexed events in real time and c) the use of nanoparticle-based libraries of immune modulating reagent combinations. There are three key objectives within this project: i) to use immune gene signatures to monitor disease progression and therapeutic efficacy of immunotherapy combinations on nanoparticle-based platforms, ii) to optimise the platform to encapsulate libraries of immune components for more personalised, accurate and timely delivery of the payload to its intended target and iii) to optimise the overall cancer management process of image-guided surgery followed by postoperative immunotherapy so that we can ultimately provide a lifetime of protection against cancer.

Sector Administration & Marketing

Contact Details

Company Name PERCUROS BV
Address Plesmanlaan 1 2333 Bz Leiden
Web Site https://cordis.europa.eu/project/rcn/198305/factsheet/en

8.

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

ITCC Pediatric Preclinical POC Platform – Sofia ref.: 116064

  • 17 Million
  • Germany
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ITCC Pediatric Preclinical POC Platform – Sofia ref.: 116064
Company Name DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Funded By 38
Country Germany , Western Europe
Project Value 17 Million
Project Detail

Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the facts that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs. To address this high, as yet unmet clinical need, we have formed the ITCC-P4 consortium consisting of academic and commercial partners from 8 European countries and covering the full spectrum of qualifications needed for quality-assured preclinical drug development including expertise in patient derived models, histopathology, in vivo pharmacology, bioinformatics and data management, centralized testing capabilities, medical expertise regarding the entities in question, regulatory knowledge, and project management of large consortia. With this consortium in a public-private partnership with the participating pharma companies we strongly believe to be ideally positioned to greatly expedite the development of more precise and efficacious drugs for children with malignant solid tumors

Sector Administration & Marketing

Contact Details

Company Name DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Address Im Neuenheimer Feld 280 69120 Heidelberg
Web Site https://cordis.europa.eu/project/rcn/210764/factsheet/en

9.

PERCUROS BV

Personalised Postoperative Immunotherapy To Improving Cancer Outcome and improving quality of life

  • 2 Million
  • Netherlands The
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Personalised Postoperative Immunotherapy To Improving Cancer Outcome and improving quality of life
Company Name PERCUROS BV
Funded By 38
Country Netherlands The , Western Europe
Project Value 2 Million
Project Detail

During this RISE project we aim to develop nanoparticle-based encapsulated libraries of different immunotherapeutic biomolecules for treatment after surgery as part of a novel cancer management strategy. The current state-of-art for the management of cancer starts with surgery, after identification of an accessible tumour mass. Surgery remains an effective treatment option for many types of cancer today and it is considered curative treatment for most solid tumours. It forms part of a multidisciplinary approach used in conjunction with radiotherapy or chemotherapy. These approaches, however, have several limitations, including inability of surgical resection to affect distal metastatic disease, toxicity to healthy tissues with chemotherapy and lack of effectiveness of radiation therapy in more aggressive tumours. The observation that cancer can relapse months or years after initial surgery implies that micrometastases still resides within the body in a latent state. Our proposal is to take cancer therapy to beyond state-of-art by implementing techniques which will take us into new directions. This includes a) new methods to identify immune gene profiles and biomarkers b) transgenic mouse models where the complex interactions that underlie immune function can be visualised as multiplexed events in real time and c) the use of nanoparticle-based libraries of immune modulating reagent combinations. There are three key objectives within this project: i) to use immune gene signatures to monitor disease progression and therapeutic efficacy of immunotherapy combinations on nanoparticle-based platforms, ii) to optimise the platform to encapsulate libraries of immune components for more personalised, accurate and timely delivery of the payload to its intended target and iii) to optimise the overall cancer management process of image-guided surgery followed by postoperative immunotherapy so that we can ultimately provide a lifetime of protection against cancer.

Sector Administration & Marketing

Contact Details

Company Name PERCUROS BV
Address Plesmanlaan 1 2333 Bz Leiden
Web Site https://cordis.europa.eu/project/rcn/212968/factsheet/en

10.

THE UNIVERSITY OF MANCHESTER

Elucidating the role of ultraviolet radiation in melanoma

  • 2 Million
  • United Kingdom
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Elucidating the role of ultraviolet radiation in melanoma
Company Name THE UNIVERSITY OF MANCHESTER
Funded By 38
Country United Kingdom , Western Europe
Project Value 2 Million
Project Detail

Melanoma incidence continues to increase across Europe and compared to other cancers, it disproportionately affects young people, causing a significant loss in life-years in those affected. Ultraviolet radiation (UVR) is the only environmental risk factor in melanoma, but the underlying genetic constitution of the individual also plays an important role. However, our knowledge of the gene-gene and gene-environment interactions in melanomagenesis is still very limited and here we will use various cutting-edge technologies to investigate the role of UVR in melanoma initiation and progression. We have developed mouse models of UVR-driven melanoma that closely mimic UVR-driven melanoma in humans and these provide an unprecedented opportunity to dissect how different wavelengths and patterns of UVR exposure affect melanomagenesis. We propose a multidisciplinary programme of work to examine how host genetic susceptibility factors and responses such as DNA damage repair and inflammation affect melanoma development and progression following UVR exposure. We will integrate knowledge from our animal experiments with epidemiological, histopathological, clinical, and genetic features of human tumours to improve stratification of human melanoma and thereby assist clinical management of this deadly disease. Our overarching aim is to develop a validated stratification approach to melanoma patients that will assist in the development of effective public health campaigns for individuals at risk across Europe.

Sector Administration & Marketing

Contact Details

Company Name THE UNIVERSITY OF MANCHESTER
Address Oxford Road M13 9pl Manchester
Web Site https://cordis.europa.eu/project/rcn/198731/factsheet/en

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