Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : THERA-LEGO (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Université Grenoble Alpes — Pays : France — Rôle : PI
Acronyme de l'entité : UGA
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cancer remains a major cause of mortality worldwide, with projections estimating that 40% of population will be diagnosed with a form of cancer during their lifetime. Despite significant progress in treatment modalities, current therapeutic regimens are still deficient due to intolerable side effects, while stray cancer cells often escape destruction. Immunotherapy-based approaches certainly represent the most promising alternatives in this area although very limited approaches are available. In addition, major issues remain to be addressed such as the lack of efficiency and autoimmune toxicity for a large population of patients. In the ERC Consolidator grant “LEGO”, we have demonstrated that fully synthetic structures with unprecedented combinations have immunological properties against cancers. We have developed a “molecular LEGO” approach to construct Antibody Recruiting Glycodendrimers (ARGs) embedded with key structural parameters and capable of redirecting endogenous antibodies present in the human bloodstream against tumors without preliminary immunization. Among a variety ARGs, we have identified two lead compound that: 1/ recruit natural Abs with a cluster of oligosaccharides; 2/ target cancer receptors with a cluster of peptides; 3/ promote the formation of a ternary complex between natural Abs and cancer cells; 4/ promote up to 60% of cytotoxicity towards cancer cells in vitro. Within THERA-LEGO, we aim to investigate the commercial feasibility and the in vivo properties of our lead compounds (toxicity, stability, biodistribution, pharmacokinetics/dynamics, immunogenicity) in humanized mice models, to facilitate the transfer of the technology to a company and the initiation of clinical development. The work to be done in this project will advance our assets from a Technology Readiness Level (TRL) of 3 to 5 and will enable us to create an exploitation strategy (relying either on commercialization through own spin-off or licensing to a pharma company).

Mots-clés : immunotherapy,cancer,antibody recruiting glycodendrimers,supramolecular chemistry,preclinicat studies,transfer of the technology
Projet ERC : INGSIGHT (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Maastricht University — Pays : Pays-Bas — Rôle : PI
Acronyme de l'entité : UM
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cancer remains one of the deadliest diseases and most deaths are due to treatment failure and metastasis. Tumor resistance and patient outcome are strongly associated with tumor heterogeneity, which is promoted by the self-renewing and multipotent cancer stem cells (CSC) and by limitations in oxygen availability generating hypoxic areas within the tumor microenvironment. The NOTCH signaling pathway is one CSC pathways frequently deregulated in human cancers but also essential in many normal tissues. Given the widespread involvement in human cancers, many attempts have been made to target NOTCH (e.g. γ-secretase inhibitors, GSIs) and the hypoxic regions in the tumor (e.g. hypoxia-activated prodrugs, HAPs) in patients. However, to date, GSIs and HAPs have not been successful in clinical studies due to limited anti-tumor responses and dose-limiting side-effects in healthy tissues. As part of the ERC project DIRECT, I have leveraged our newfound knowledge on NOTCH signaling and hypoxia in tumors to develop two classes of novel NOTCH /g-secretase inhibitors (GSI) that enable tumor cell-specific inactivation of the NOTCH pathway (PSEN2-inhibitor) or by generating a dual-specificity NOTCH-inhibitor that is only released and active in hypoxic tumor regions (HyGSI) without affecting normal tissues. This ERC PoC INGSIGHT will assess the technical and commercial feasibility of these two novel inhibitors of the NOTCH pathway with the potential to radically improve cancer therapy outcomes. We will demonstrate the maximum tolerated dose in normal tissues and the therapeutic effects using five different tumor models. We will solidify our IP position and we will conduct a market, competitor, and stakeholder analysis to ensure the selection of the most optimal business strategy. As a result, we will gain technical and commercial Proof-of-Concept to determine the best route towards the commercialization of the PSEN2 inhibitor and/or HyGSI dual-specificity inhibitor.

Mots-clés : notch,cancer therapy,treatment toxicity,hypoxia,tumour microenvironment,secretase,dual targeting drugs
Projet ERC : Unusual-IV (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Cenya imaging b.v. — Pays : Pays-Bas — Rôle : PI
Type d'entité : Organismes privés (hors enseignement)
Financement ERC de l'entité : 150000.0 €

Cancer. Cardiovascular disease. Autoimmune disease. Neurological disease. Rheumatoid arthritis. What do these diseases have in common? -Chronic inflammation. In recognition of this, the NIH organised a focus session on the current clinical needs around inflammation in 2019, stating “Tools to locate and monitor inflammation are critical for developing effective interventions to arrest inflammation and promote its resolution. Clinical speakers described their needs for image‐based capabilities ... to guide treatment planning and undertake necessary interventions…All speakers agreed that multiple inflammatory measures should be acquired longitudinally to comprehend the dynamics of unresolved inflammation that leads to disease development.” As an example, atherosclerosis- the #1 killer in developed countries- is now known to be a chronic inflammatory disease . Mounting clinical evidence suggests that effective treatment requires a reduction in both LDL levels (cholesterol) and underlying inflammation. However, a simple reduction in inflammation, measured by serum markers, has not proven successful in the clinic . Thus, as also found by the NIH workshop, treatment plans must take into account the inflammation status in the vessel walls in a longitudinal manner, which cannot be measured by blood tests. This is no small task, as chronic inflammation is often asymptomatic until disease has developed. Pubmed has over 36,000 review articles on chronic inflammation. The ultimate goal is to have clinical noninvasive biomarkers of inflammation that can help in diagnosis, predict outcome and assess response to therapy or preventative strategy. Overall, there is an unmet need to noninvasively diagnose inflammation, that can be used in conjunction with conventional biofluid and biopsy markers. This is particularly the case when treatment includes longterm preventative lifestyle changes. Noninvasive clinical imaging could be the solution.

Mots-clés : inflammation,imaging,nanoparticles,clinical trials,personalised medicine
Projet ERC : NOVCARBFIX (Horizon 2020, appel 2014, Consolidator grants)
Domaine scientifique : Life Science
Panel : Integrative Biology: from Genes and Genomes to Systems
Entité participante : Weizmann Institute of Science — Pays : Israël — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1999843.0 €

Carbon fixation is a prerequisite for accumulating biomass and storing energy in most of the living world. As such, it supplies our food and dominates land and water usage by humanity. In agriculture, where water and nutrients are abundant, the rate of carbon fixation often limits growth rate. Therefore increasing the rate of carbon fixation is of global importance towards agricultural and energetic sustainability. What are the limits on the possible rate of carbon fixation? Attempts to improve RuBisCO, the key enzyme in the Calvin-Benson cycle, have achieved only limited results. My lab focuses on trying to overcome this global challenge by building synthetic pathways for carbon fixation. We create a computational framework that designs and scores pathways and creates step-wise selection strategies for in-vivo experimental implementation. Our most promising synthetic carbon fixation pathways are found to utilize the highly effective carboxylating enzyme, PEP carboxylase. We experimentally test these pathways in the most genetically tractable context by constructing an E.coli strain that depends on atmospheric CO2 fixation. We will gradually incorporate the pathways, initially as essential reaction steps for biomass production, and finally with CO2 as sole carbon input of the cell. As a stepping-stone towards this challenging goal, we will construct an autotrophic E.coli strain that uses the Calvin-Benson cycle. We systematically convert this synthetic biology grand challenge into a gradual evolutionary ladder with independently selectable steps. We recently achieved key steps in the ladder, such as semi-autotrophic growth, serving as powerful proofs of concept. The proposed research will advance our basic-science understanding of evolutionary plasticity of metabolic pathways. It also paves the way for a hybrid rational-design/experimental-evolution approach to revisit and advance the capacity of metabolism for agricultural productivity and renewable energy storage.

Mots-clés : carbon fixation cycles,metabolic pathways
Projet ERC : Mini-HEART (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : University of Padua — Pays : Italie — Rôle : PI
Acronyme de l'entité : UNIPD
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Cardiac disease causes morbidity and mortality as frequently as cancer. Predicting cardiac arrhythmia and cardiac failure, understanding multicellular (patho)physiological mechanisms, and devising new treatments represent unmet needs in the field. Human induced pluripotent stem cells (hiPSC) could revolutionise the way we study human disease but unfortunately, they still fall short in recapitulating variable phenotypes and complex cardiovascular diseases. This is partly due to functional immaturity of hiPSC-derived cardiac tissues, shortage of methods for accurate functional analysis and inability to identify cell-type specific contributions to disease pathology. I will address these challenges in Mini-HEART. We recently assembled novel three-dimensional multi-cellular cardiac microtissues as an important step towards full maturation and used these to demonstrate that cardiac disease mutations might directly affect non-myocyte cardiac cells. However, application of hiPSC microtissues to precision medicine remains to emerge. Using a multidisciplinary approach, I will combine isogenic hiPSC, their differentiation into distinct cell types of the heart, multifaceted biophysical assays, and tissue engineering to prove cell-type causality of disease and identify new molecules targeting the culprit cells to rescue the disease phenotype. I plan to use our unique complex hiPSC-cardiac microtissue to 1) identify and synthetically enhance maturation mechanisms; 2) reveal late arrhythmic and fibrotic phenotypes; 3) dissect cell-type specific contributions to complex cardiac diseases, including the role of macrophages and sympathetic nerves; 4) test two therapeutic strategies based on drug-tailoring and gene editing, to modulate the disease phenotype. Together, Mini-HEART will create new opportunities for designing novel biomedical tools to i) capture phenotypic changes, ii) reveal (patho)physiological mechanisms and ii) develop new therapeutic approaches for heart disease.

Mots-clés : cardiac arrhythmia,sudden death,human induced pluripotent stem cells,cardiac organoids,channelopathies,cardiomyopathies
Projet ERC : MEGFIB (Horizon 2020, appel 2019, Proof of concept grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Hannover Medical School — Pays : Allemagne — Rôle : PI
Acronyme de l'entité : MHH
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Cardiac fibrosis is a hallmark of and mechanistically involved in heart failure; a disease will high clinical unmet need and fundamental socioeconomic importance. Specific treatments of cardiac fibrosis are lacking. RNAs that do not code for proteins comprise a large portion of the human genome. These so-called noncoding RNAs are emerging as important players in disease pathogenesis, yet their functional roles are ill understood. Our group currently pioneered first clinical testings on noncoding RNA inhibitors in heart failure patients showing the enormous clinical translational potential of such next-generation therapeutics. We now aim to develop a new approach to treat selected heart failure patients, which show increased signs of cardiac fibrosis. Within the ERC grant LONGHEART we have identified a lncRNA meg3 to be a novel and innovative target in heart failure pathologies with fibrosis (Circ Res. 2017 Aug 18;121(5):575-583; Fig. 1). Importantly meg3 is well conserved between rodents and humans allowing translational development. Oligonucleotide-mediated silencing of Meg3 in human cardiac fibroblasts and in vivo in mice resulted in decreased cardiac fibrosis and improved diastolic performance of the heart. Within MEGFIB, we now aim to advance these valuable research results on meg3-based improvements of cardiac fibrosis in mice towards commercial proof-of-concept. Important next steps are a) translation of the efficacy to human cells and tissues and b) sophisticated market analysis, c) IP strategy development and d) business development activities to maximize the value of the projects’ results. The outcome of our activities will be consolidated into a business plan for presenting our proposition to strategic partners, such as Cardior Pharmaceuticals or venture capitalists (VCs). We are proposing a unique RNA-based approach that offers a new opportunity to revolutionize medical practice, improve patient care and will reduce costs in the heart failure care.

Mots-clés : noncoding rnas,heart failure,new therapies
Projet ERC : MATRIX (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Hospital Universitario Fundación Jiménez Díaz — Pays : Espagne — Rôle : Partner
Acronyme de l'entité : FJD
Type d'entité : Recherche
Financement ERC de l'entité : 525937.5 €

Cardiac toxicity is one of the most frequent serious side effects of cancer therapy, affecting up to 30% of treated patients. Cancer treatment-induced cardiotoxicity (CTiCT) can result in severe heart failure. The trade-off between cancer and chronic heart failure is an immense personal burden with physical and psychological consequences. Current therapies for CTiCT are suboptimal, featuring poor early detection algorithms and nonspecific heart failure treatments. Based on our recently published results and additional preliminary data presented here, we propose that CTiCT is associated with altered mitochondrial dynamics, triggering a cardiomyocyte metabolic reprogramming. MATRIX represents a holistic approach to tackling mitochondrial dysfunction in CTiCT. Our hypothesis is that reverting metabolic reprogramming by shifting mitochondrial substrate utilization could represent a new paradigm in the treatment of early-stage CTiCT. By refining a novel imaging-based algorithm recently developed in our group, we will achieve very early detection of myocardial damage in patients treated with commonly prescribed cancer therapies, long before clinically used parameters become abnormal. Such early detection, not available currently, is crucial for implementation of early therapies. We also hypothesize that in end-stage CTiCT, mitochondrial dysfunction has passed a no-return point, and the failing heart will only be rescued by a strategy to replenish the myocardium with fresh healthy mitochondria. This will be achieved with a radical new therapeutic option: in-vivo mitochondrial transplantation. The MATRIX project has broad translational potential, including a new therapeutic approach to a clinically relevant condition, the development of technology for early diagnosis, and advances in knowledge of basic disease mechanisms.

Mots-clés : heart failure,cardiotoxicity,cardio oncology,myocardium,therapies
Projet ERC : MATRIX (Horizon 2020, appel 2018, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : Ministry of Health — Pays : Espagne — Rôle : PI
Type d'entité : Recherche
Financement ERC de l'entité : 1473437.5 €

Cardiac toxicity is one of the most frequent serious side effects of cancer therapy, affecting up to 30% of treated patients. Cancer treatment-induced cardiotoxicity (CTiCT) can result in severe heart failure. The trade-off between cancer and chronic heart failure is an immense personal burden with physical and psychological consequences. Current therapies for CTiCT are suboptimal, featuring poor early detection algorithms and nonspecific heart failure treatments. Based on our recently published results and additional preliminary data presented here, we propose that CTiCT is associated with altered mitochondrial dynamics, triggering a cardiomyocyte metabolic reprogramming. MATRIX represents a holistic approach to tackling mitochondrial dysfunction in CTiCT. Our hypothesis is that reverting metabolic reprogramming by shifting mitochondrial substrate utilization could represent a new paradigm in the treatment of early-stage CTiCT. By refining a novel imaging-based algorithm recently developed in our group, we will achieve very early detection of myocardial damage in patients treated with commonly prescribed cancer therapies, long before clinically used parameters become abnormal. Such early detection, not available currently, is crucial for implementation of early therapies. We also hypothesize that in end-stage CTiCT, mitochondrial dysfunction has passed a no-return point, and the failing heart will only be rescued by a strategy to replenish the myocardium with fresh healthy mitochondria. This will be achieved with a radical new therapeutic option: in-vivo mitochondrial transplantation. The MATRIX project has broad translational potential, including a new therapeutic approach to a clinically relevant condition, the development of technology for early diagnosis, and advances in knowledge of basic disease mechanisms.

Mots-clés : heart failure,cardiotoxicity,cardio oncology,myocardium,therapies
Projet ERC : HEART.FM (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of London — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 17677.94 €

Cardiovascular disease is the world’s leading cause of death, and hypertension is its foremost medical risk factor. Reducing blood pressure in hypertensive patients has positive cardiovascular effects, and music listening offers non-pharmacological ways to regulate heart rate and blood pressure. Presently, the most effective way to administer music inventions with long-lasting effects is labor-intensive and relies on professional therapists’ intuitions, making it non-scalable to large cohorts. HEART.FM is an app-creation initiative to democratize access to personalized music medicine interventions, informed by physiological feedback. Current music therapy apps fail to address the subjectivity and specificity inherent in individual music response; a gap further exists between music therapy apps and physiological feedback. By leveraging advances in wearable ECG monitors and portable blood pressure sensors, HEART.FM will offer music therapy based on individual users’ physiological feedback around musical change points and transitions, which correspond to emotionally salient moments in music listening. HEART.FM exploits the music structure knowledge and cross-modal music-physiology analysis methods developed and trialed in the ERC project COSMOS to advance the state of the art by linking physiological feedback with computational music structure analysis to provide personalized music listening therapy to achieve targeted autonomic nervous system responses. A development goal will be to make HEART.FM ready for large-scale deployment in randomized, controlled research trials that can establish music-hypertension cause-effect relationships for healthy individuals as well as hypertensive patients. HEART.FM will benefit the research community by offering a crowdsourced portal for collecting research data in cardiovascular disease and music-based preventative therapies. The PoC will explore commercialization and market solutions in both music and medical sectors.

Mots-clés : personalized music medicine,computational music structure analysis,software system,hypertensive heart disease
Projet ERC : HEART.FM (Horizon 2020, appel 2020, Proof of concept grants)
Domaine scientifique : Social Sciences and Humanities
Panel : Cultures and cultural production
Entité participante : University of London — Pays : Royaume-Uni — Rôle : Partner
Acronyme de l'entité : U. London
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 38578.0 €

Cardiovascular disease is the world’s leading cause of death, and hypertension is its foremost medical risk factor. Reducing blood pressure in hypertensive patients has positive cardiovascular effects, and music listening offers non-pharmacological ways to regulate heart rate and blood pressure. Presently, the most effective way to administer music inventions with long-lasting effects is labor-intensive and relies on professional therapists’ intuitions, making it non-scalable to large cohorts. HEART.FM is an app-creation initiative to democratize access to personalized music medicine interventions, informed by physiological feedback. Current music therapy apps fail to address the subjectivity and specificity inherent in individual music response; a gap further exists between music therapy apps and physiological feedback. By leveraging advances in wearable ECG monitors and portable blood pressure sensors, HEART.FM will offer music therapy based on individual users’ physiological feedback around musical change points and transitions, which correspond to emotionally salient moments in music listening. HEART.FM exploits the music structure knowledge and cross-modal music-physiology analysis methods developed and trialed in the ERC project COSMOS to advance the state of the art by linking physiological feedback with computational music structure analysis to provide personalized music listening therapy to achieve targeted autonomic nervous system responses. A development goal will be to make HEART.FM ready for large-scale deployment in randomized, controlled research trials that can establish music-hypertension cause-effect relationships for healthy individuals as well as hypertensive patients. HEART.FM will benefit the research community by offering a crowdsourced portal for collecting research data in cardiovascular disease and music-based preventative therapies. The PoC will explore commercialization and market solutions in both music and medical sectors.

Mots-clés : personalized music medicine,computational music structure analysis,software system,hypertensive heart disease