À l’Inserm, la lutte contre la pandémie de Covid-19 se poursuit

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Back at the start of the pandemic, Inserm, through its REACTing consortium, set up Discovery: a European clinical trial to evaluate the efficacy of four antiviral drugs repurposed for the treatment of patients hospitalized with COVID-19 (remdesivir, hydroxychloroquine, lopinavir and interferon beta-1a). In parallel, the World Health Organization (WHO) set up Solidarity, a major consortium of clinical trials also aimed at testing the efficacy of these four treatments. Discovery then joined forces with Solidarity to help supply it with robust and rigorous data. The initial results of Solidarity have now been published in the New England Journal of Medicine.
Launched in March 2020 under the aegis of Solidarity – the World Health Organization (WHO) global clinical trials – Discovery is a clinical trial to study efficacy and safety. It is the only large-scale European academic trial of COVID-19 treatments.
Focusing on patients hospitalized with severe COVID-19 in France and other European countries, this trial is both randomized (the treatments are randomly assigned to the participants) and open-label (the patients and their caregivers know which treatment they have been allocated). The data obtained in Discovery form part of the data analyzed within the framework of Solidarity and have been presented in the study by the New England Journal of Medicine.
The analysis covers 11,330 adult patients in 405 hospitals across 30 countries and includes Solidarity’s “daughter trials” (with one of the main contributors being Discovery). The patients were assigned to different groups in order to receive one of the following regimens:
The results suggest that none of these treatments have an effect on the clinical improvement of patients. None of them significantly reduce overall mortality, the risk of having to initiate mechanical ventilation, or the duration of hospitalization.
However, within the framework of Solidarity and Discovery, it has nevertheless been decided to continue enrolments in the remdesivir group. Indeed, the meta-analysis presented in the study suggests that although mortality is not reduced in the mechanically ventilated patients in intensive care having received remdesivir, it does show that remdesivir may slightly reduce mortality in the subgroup of hospitalized patients who do not require mechanical ventilation. In addition, while a scientific consensus is emerging as to the lack of efficacy of the other therapeutic combinations tested in Solidarity, data published in other studies remain contradictory on the subject of remdesivir.
The decision by the Discovery investigators to continue enrolments in this group has therefore been made with the aim of obtaining new data in order to decide one way or the other on the utility of remdesivir in severe COVID-19.
©Photo by Kelly Sikkema on Unsplash
A team of researchers from Inserm, CNRS, Université Grenoble Alpes and Barcelona Institute for Global Health has shown that prenatal and postnatal exposure to various chemical pollutants is linked to decreased respiratory function in children. These results, based on the concept of the exposome (defined as the totality of an individual’s environmental exposures from conception until old age), were obtained as part of the European HELIX project and have been published in The Lancet Planetary Health.
With the changes in our lifestyles and the development of synthetic chemistry, exposure to environmental contaminants has become multiple and complex. Pregnancy and the early years of life are recognized as being periods of high sensitivity to environmental factors, with potential lifetime health consequences for the child. Researchers from Inserm, CNRS, Université Grenoble Alpes and Barcelona Institute for Global Health have measured a large number of environmental factors to which children are exposed – including through maternal exposure during pregnancy –, and which are defined as the “early life exposome”.
The researchers collected data from prenatal and postnatal exposures related to the external environment (pollution of the air with fine particles, noise…), chemical contaminants (endocrine disruptors, metals, persistent organic pollutants…), and lifestyle (diet…) in over 1,000 pregnant women and their children in six European countries. Through 85 prenatal exposures and 125 postnatal exposures, a snapshot of the early-life environment was established for each child. The pregnant women and the children had generally been exposed to dozens of chemical substances at variable levels. Over two-thirds of the chemical exposure biomarkers had levels detectable in at least 9 women or 9 children out of 10.
This study, one of the very first large-scale implementations of the exposome approach, suggests links between pre- and postnatal exposure to chemical substances and deteriorated respiratory function in children. Valérie Siroux, Inserm researcher and joint-coordinator of the study specifies: “Identifying the risk factors of decreased early-life respiratory function is important because lung development is a determinant factor not just of a child’s lifetime respiratory health, but also their general health”.
This exposome approach must be seen as an initial selection step making it possible to identify questionable exposures for which more specific research is needed.
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The respective classifications of the European Patent Office (EPO) and France’s National Industrial Property Institute (INPI), which have just published their annual rankings for 2017, have confirmed Inserm’s ability to innovate. Inserm placed first among patent applicants in the pharmaceutical sector for the second year in a row, yet again leading the rankings of European applicants in this sector, ahead of both industrial manufacturers and academic institutions. Furthermore, the Institute was in 30th place – having moved up five places – in the INPI’s “patents in all fields” ranking, confirming its research teams’ excellence and productivity in innovation.
For the second year in a row, Inserm is the leading European patent applicant in the pharmaceutical sector, with 107 patents filed, or three more patents than last year, staying ahead of the sector’s major industrial manufacturers. In the biomedical sector, Inserm has retained its place as the leading academic applicant, with 266 patents filed. In the biotechnology sector, Inserm is in fourth place among European patent applicants, with 92 applications. Lastly, Inserm has maintained its presence as one of the top 100 patent applicants worldwide, taking all structures and fields together. This significant number of patents filed shows how animated research is at Inserm, and how strongly and regularly the Institute contributes to innovation. These patents comply with all international quality standards thanks to a fruitful collaboration between Inserm’s research teams and Inserm Transfert’s value-creation specialists.
In the French National Industrial Property Institute’s (INPI) ranking of patent applicants in France, Inserm has moved up five places, ranking 30th among the main patent applicants in all fields.
“As a leading biomedical research Institute, our objective is to increase the effective and productive dialogue between academics and industry, since we know that today, cooperation between these two worlds is more important than ever. The excellent results in these two rankings is proof of our fully operational dynamic of success, which we will continue to build on in the months to come,” states Prof. Yves Lévy, Inserm’s CEO.
With a world-wide, diversified portfolio of 1,673 patent families, Inserm has a wealth of protected innovations, for which the creation of value is entrusted to Inserm Transfert, its private subsidiary under public service delegation. Inserm Transfert is in charge of transferring the knowledge derived from Inserm’s research laboratories to patients, industrial manufacturers, and the market. This excellent placement in the EPO ranking shows the innovation potential of Inserm’s researchers as well as the ability of Inserm and its subsidiary, Inserm Transfert, to protect advances in French research of excellence in a context of fierce international competition. The quality, strength, and solidity of the portfolio of patents on the global scene remain the keys for successful transfer, leading to the emergence of the treatments of tomorrow, the creation of value from Inserm’s academic research, and the consolidation of the French economic fabric of innovation.
(c) Inserm/Depardieu, Michel
Very premature infants, born before 32 weeks of gestation, (8th month of pregnancy), represent 1–2% of all births. For these neonates, the risks of mortality and long-term neurological disorders are higher than for infants born at full term. It is essential to provide them with appropriate care in order to guarantee them better health.
The EPICE project created a population cohort in 2011, comprising all very premature infants from 19 regions in 11 countries of the European Union (Belgium, Denmark, Estonia, France, Germany, Italy, the Netherlands, Poland, Portugal, Sweden and the United Kingdom). The goal of the project is to evaluate the “evidence-based medical practices” applied to these infants.
Evidence-based medicine, which takes research data, clinical expertise, and patient needs into consideration, enables health professionals to make care choices based on proven clinical efficacy. In this study, Jennifer Zeitlin, Inserm Research Director, studied four of these medical practices in particular, in order to measure their impact on neonatal mortality:
– transfer of pregnant women to specialised centres designed to accommodate very premature infants,
– antenatal administration of corticosteroids (for maturation of the lungs),
– prevention of hypothermia,
– administration of surfactant (an essential substance for respiratory function that lines the pulmonary alveoli) within 2 hours after birth, or nasal positive pressure ventilation, for infants born before 28 weeks of gestation
While there was frequent use of each practice individually (75–89%), only 58% of very premature infants received all four recommended practices.
The study simulated two models to measure the impact of this inadequate care. If every infant had received all four recommended practices, mortality would have been reduced by 18%. These results demonstrate the importance of evidence-based medical care in improving the health of very premature infants.
“Effective Perinatal Intensive Care in Europe: translating knowledge into evidence-based practice”
The EPICE project is dedicated to the medical care of very preterm infants born before 32 weeks of gestation, in eleven European countries. The aim of the project is to assess practices in order to improve health care for this population of high risk babies.
The EPICE project was launched in 2011 and has been supported by the European Union (FP7) for five years. It is coordinated by Inserm, just like 27 other European “health” projects. The project involves 12 partners and 6 associate partners, based in 11 European countries.
The 12 partners:
Inserm (coordinator), France
SPE, Belgium
Hvidore Hospital, Denmark
Universitas Tartuensis, Estonia
Philipps Universität Marburg, Germany
Bambino Gesu Ospedale Pediatrico, Italy
Laziosanita Agenzia Di Sanita Pubblica, Italy
Radboud University Nijmegen Medical Centre, the Netherlands
Poznan University of Medical Sciences, Poland
U.Porto, Portugal
University of Leicester, United Kingdom
Karolinska Institutet, Sweden
EPICE in France
The EPICE project in France is part of a national study entitled EPIPAGE 2 (an epidemiological study on very preterm babies). It is a cohort study of very preterm infants, launched in 2011 in the 22 regions of mainland France and the French overseas departments. The study will monitor over 6000 premature children up to the age of 11 to 12. Three regions in France: Ile-de-France, Nord-Pas-de-Calais and Bourgogne participate in EPICE project.
The EPIPAGE 2 project is managed by the Inserm unit 953 (“Epidemiological research into perinatal health and the health of women and infants”), in collaboration with team 2, from UMRS 1027, directed by Dr Catherine Arnaud (Perinatal epidemiology, handicap of child and health of adolescents.
For further information on this study: www.epipage2.inserm.fr (Head of studies: Pierre-Yves Ancel, Inserm U953)
[1] http://presse.inserm.fr/en/optimizing-the-care-of-very-preterm-infants-a-collective-european-initiative/4699/
An international group of scientists from 6 countries bring together their expertise to improve diagnosis and therapeutic care for primary and secondary forms of arterial hypertension. ENS@T-HT, which is coordinated by Maria-Christina Zennaro, Research Director at Inserm (Paris Cardiovascular Research Center), was officially launched this month in Paris and will last 5 years.
Hypertension affects up to 45% of the general population and is responsible for 9.4 million deaths per year worldwide. Even small rises in blood pressure are associated with increased risk of stroke and heart disease. However, despite a large array of available treatments, blood pressure is still not properly controlled in many patients.
Approximately 10% of current hypertension cases could be treated and cured if properly diagnosed. These include disorders of the adrenal gland that increase the production of hormones affecting blood pressure. Correct identification of these disorders is crucial to proper management of the underlying disease and prevention of cardiovascular complications. However, due to the complexity of diagnosis, proper treatment of these conditions can be delayed by several years, exposing patients to increased cardiovascular and metabolic risk and diminished quality of life.
ENS@T-HT is a five-year-long European H2020 research project created to tackle these issues. It received funding of €7.6m and involves 13 academic institutions from France, Germany, Italy, the United Kingdom, the Netherlands and Australia.
Maria-Christina Zennaro, coordinator of ENS@T-HT (Inserm Unit 970, Paris Cardiovascular research center) says: « The ambition of this project is twofold: first we want to establish omics-derived biomarkers and validate their accuracy in the diagnosis of patients with adrenal forms of hypertension. Second, and most importantly for patients, we want to use these biomarkers to accelerate and optimize the diagnosis and management of these conditions. We can then stratify those patients who could most benefit from specific targeted treatment ».
— In an initial exploratory phase partners will establish omics-derived signatures of patients with PA, PPGL and CS through bioinformatics modelling of large datasets derived from multiple platforms.
— The signatures will be validated as stratification biomarkers by establishing reference values and variability in healthy controls.
— They will subsequently be used in a prospective clinical study to identify endocrine forms of hypertension and to stratify patients with arterial hypertension. The usefulness and cost-effectiveness of this approach will be evaluated in comparison to current standard of care outcomes and costs.
ENS@T-HT is based on the exploitation of unique cohorts of patients with PA, PPGL and CS recruited by reference centers for adrenal disorders organized within the European Network for the Study of Adrenal Tumors ENS@T (www.ensat.org). ENSAT-HT will take advantage of the prospective collaboration of six European Society of Hypertension ESH Centres of Excellence (http://www.eshonline.org/), providing a unique capability for the recruitment and workup of a large cohort of hypertensive patients.
Website : http://www.ensat-ht.eu/
An Ipsos survey for Inserm
The French National Institute of Health and Medical Research (Inserm) is currently the leading biomedical research organisation in Europe, and plays a key role in developing European research. To mark its 50th anniversary, Inserm wanted to assess the perceptions of Europeans regarding biomedical research.
To create this European panorama, Ipsos carried out an Internet survey of over 4,000 Europeans (with 1,001 French, 1,004 German, 1,001 Italians and 1,005 British respondents) from 10 to 23 January 2014. Representative samples were obtained from each country involved using quota sampling.
According to results, health is still the area of research news that interests the greatest number of Europeans. This survey confirms the genuine confidence of Europeans regarding biomedical research and its players, at a time of moroseness and cynicism. Although they are aware that they do not understand all of its ramifications, they see it as a source of hope for themselves and their children, as well as a source of pride for their country.
The most memorable medical innovations for Europeans in the last 50 years have been organ transplants, medical imaging, and gene therapies.
Health, a theme of major interest for Europeans
Biomedical research is above all a synonym for hope
A high degree of confidence in researchers
A limited level of information and knowledge, but a questioning attitude nonetheless
The United States model, and development of European research funding
Organ transplants, medical imaging and gene therapy considered the most important medical innovations in the last 50 years
As part of the European project HabEat (2010-2014), coordinated by INRA and involving 10 scientific partners, researchers have made a step forward in the understanding of how eating behaviours and preferences form in early life. On March 31st and April 1st in Dijon (France), a symposium presents the results and recommendations for early childhood professionals and parents.
When looking at eating behaviours and preferences, even if it’s not all over at the end of early childhood, the first two years of life are of utmost importance regarding the development of eating behaviours in children, with a key period when solid foods are introduced. The collaborative project HabEat had the aim of better understanding the determinants of the formation of eating habits through two distinct approaches, epidemiological on one side and experimental on the other.
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Data from 18 000 mother-child pairs followed from birth to at least 4 years of age
Four large European cohorts have given insight into usual early feeding practices. The factors associated to the frequency of consumption of fruits and vegetables at various times during the establishment of the food repertoire were particularly investigated.
18 studies involving, in total, nearly 2000 children between 6 months and 6 years of age
The experimental part of the project comprised two sections. The first one primarily focused on key learning mechanisms, and concerned children from the beginning of complementary feeding (around 6 months) to 3-year-olds. The second studied different strategies aimed at increasing vegetable consumption beyond 3 and until 6 years of age.
Main results
Longer breastfeeding was associated with higher frequency of fruit and vegetable consumption in later childhood.
Introducing a variety of pureed vegetables at the beginning of the complementary feeding period facilitates the acceptance of novel vegetables in the short and medium term.
Repeatedly giving a novel vegetable is sufficient for increasing its consumption even in children who are ‘picky’ about food. However, giving already known vegetables repeatedly to kids between 3 and 6 is not efficient for increasing their consumption.
It is difficult to increase intake of an already familiar vegetable in older children (3 to 6). One strategy that seems to help is to let the child choose between two vegetables.
As early as 3 years of age, if a snack is offered before a meal, or if palatable foods are available after a meal, some children increase their total energy intake. This could lead over time to the child becoming overweight.
Recommendations for early childhood professionals and parents
The scientific results of this project have been translated into recommendations that will be addressed to early childhood professionals, pediatricians, politicians in charge of nutritional policies, and to agri-food industrials. These recommendations will be discussed during the symposium.
A guide for parents has been designed on the basis of the project’s results and of prior data.
HabEat received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under the grant agreement n°245012-HabEat.
The cohorts:
ALSPAC (UK), 14 000 mother-child pairs, pregnant women were recruited from 1991 to 1992 and their children followed-up until 13 years of age
EDEN (FR), 2 000 mother-child pairs, pregnant women recruitedfrom 2003 to 2006, and their children followed-up until 5 years of age
Generation XXI (Portugal), about 8 500 mother-child pairs, pregnant women recruited from 2005 to 2006, and their children followed-up until 4 years of age
Europrevall (Greece), about 1 000 mother-child couples recruited from 2005 to 2007, and their children followed-up until 4 years of age.
The international consortium A-PARADDISE (Anti-Parasitic Drug Discovery in Epigenetics), coordinated by Inserm, has just obtained funds of €6 million from the European Commission to conduct large-scale testing of innovative therapies against four neglected parasitic diseases: schistosomiasis, leishmaniasis, Chagas disease and malaria. The researchers have a common objective: to develop new drugs against the parasites that cause these diseases. The project involves 10 European partners, 5 Brazilian partners (who operate in the region where the diseases are endemic) and 2 Australian partners. They will all be meeting on 17 and 18 March at the Institute of Genetics and Molecular and Cellular Biology (Inserm / CNRS / University of Strasbourg Joint Research Unit), to get the project started.
Schistosomiasis, leishmaniasis, Chagas disease and malaria are regarded as neglected diseases because the effort and funds put into developing new treatment and control methods have not been commensurate with their catastrophic human impact. They affect people in developing countries, essentially in Africa, the Middle East, South America and eastern Asia, in tropical and sub-tropical regions. Around one billion people are regularly exposed to these diseases, which cause almost one million deaths every year.
At present, there is no vaccine against these parasites. Furthermore, the efficacy of existing treatments is limited, either by the side effects or by the current or potential development of resistance. Consequently, the A-PARADDISE consortium, which is coordinated by Inserm and headed by Raymond Pierce – Director of Research at the Centre for Infection and Immunity in Lille – is focusing on developing new drugs against these parasitoses.
The A-PARADDISE project will use a methodology that has already been tried and tested during a previous project of a similar scale (SEtTReND), which aimed to develop drugs against schistosomiasis. The researchers investigated histone-modifying enzymes (HME), which determine the structure of the parasite’s chromosomes. It was demonstrated that some HME inhibitors induce cell death, which makes them toxic to this parasite. This research provided the proof of concept that HMEs act on the schistosomiasis parasite, and has led to the development of a bank of candidate compounds which can rapidly be tested against other human parasites.
The ultimate objective of the A-PARADDISE project is to provide several candidate treatments against the four parasites and to pave the way for clinical trials in the near future.
To ensure the success of the project, the participants were all selected for their high level of expertise in their respective fields: high-throughput screening, computer-aided screening, the production of recombinant proteins, next generation sequencing, phenotypic tests, toxicology and pharmacology.
A-PARADDISE: Anti-Parasitic Drug Discovery in Epigenetics
The A-PARADDISE project began on 1 February 2014 and will be backed by the European Union for three years (FP7, grant agreement no. 602080). It is coordinated by Inserm and includes 17 partners based in 5 European countries, Brazil and Australia:
Institut National de la Santé et de la Recherche Médicale, Group Avenir, Paris, France
Centre Européen de Recherche en Biologie et Médecine (CERBM*), France
Martin Luther Universität Halle- Wittenberg (MLU), Germany
Universidade Federal do Rio de Janeiro (UFRJ), Brazil
Universidade de Sao Paulo (USP), Brazil
Albert Ludwigs Universität Freiburg (ALU-FR), Germany
Fundação Oswaldo Cruz, Centro de Pesquisas René Rachou (Fiocruz), Brazil
Fundação Oswaldo Cruz, Instituto Carlos Chagas (Fiocruz), Brazil
Inserm Transfert SA (IT), France
KANCERA AB (KAN), Sweden
Adlego Biomedical AB (Adlego), Sweden
GriffithUniversity (GU), Australia
University of Queensland (UQ), Australia
Università degli Studi di Roma La Sapienza (UNIROMA1), Italy
University of East Anglia (UEA), Great Britain
Fundação Arthur Bernardes – Universidade Federal de Viçosa (UFV), Brazil
Institut Pasteur Paris (IPP), France
* The CERBM is the European branch of the Institute of Genetics and Molecular and Cellular Biology (IGBMC, Inserm/CNRS/Université de Strasbourg)
European cutting-edge research will be attended at the annual meeting of the American Association for the Advancement of Science (AAAS) in Chicago. Inserm will be represented by Karine Clément, scientific coordinator of the European project METACARDIS (Metagenomics in Cardiometabolic Diseases) at the session entitled “Inside out: the impact of gut flora on diabetes and obesity”.
Three leading European researchers on the gut microbiome will be present at the 2014 AAAS meeting, on Saturday 15 February, to share their recent findings on the relations between gut flora and obesity, diabetes, and cardio-metabolic diseases in general. Their findings are at the cutting-edge of one of the most innovative and challenging areas of biomedical research and could make a vital contribution to the fight against obesity and diabetes.
In recent years, the 1.5 kilos of bacteria that live inside our bodies, mainly in the gut, have proven their crucial importance for our healthy functioning. Beyond their more obvious role in digestion, they are also involved, for example, in the development of the immune system and the neuronal system, and in the onset of certain diseases.
The speakers:
Karine Clément – Professor, Institute of Cardiometabolism and Nutrition, and National Institute of Health and Medical Research (Inserm), France
Functional Genomics of Human Obesity Related to Cardiometabolic Diseases
Coordinator of the European project METACARDIS.
Sven Pettersson – Professor, Karolinska Institutet, Sweden
How Early Life Gut Flora May Contribute to Obesity and Diabetes Later in Life
Oluf B. Pedersen – Professor, University of Copenhagen, Denmark
Links Between Human Gut Microbiota and Metabolic Pathologies
Discussant: Jenny Leonard – Editor, Futurity.org, USA
http://www.futurity.org/
About this session:
http://aaas.confex.com/aaas/2014/webprogram/Session6938.html
When? Saturday, 15 February 2014 – 1:00 PM to 2:30 PM
Where? Grand Ballroom C North (Hyatt Regency Chicago)
About the 2014 AAAS annual meeting in Chicago – Feb 13-17
The AAAS Annual Meeting is a widely recognized general science event. Thousands of leading scientists, engineers, educators, policymakers, and journalists gather from around the world to discuss recent developments in science and technology. The 2014 theme, Meeting Global Challenges: Discovery and Innovation, focuses on finding sustainable solutions through inclusive, international, and interdisciplinary efforts that are most useful to society and enhance economic growth.
About CommHERE
CommHERE – www.commhere.eu – aims to increase awareness of the activities and outcomes of the various health research projects funded by the European Union. The CommHERE consortium comprises nine research institutions in six European countries, ensuring close connection with active health researchers. Stay in touch with European research with www.horizonhealth.eu