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(French) : GrippeNet.fr : bilan au pic de l’épidémie

When hypertension progresses unseen

When blood pressure is normal in the doctor’s surgery, but is high at home! This is an unknown phenomenon known as “masked hypertension”. Christophe Tzourio, Research Director of Inserm unit 708 “Neuroepidemiology” (University of Bordeaux Ségalen) studied the occurrence of masked hypertension in a population of 1500 elderly persons. Not only does it occur frequently and by definition goes undetected by doctors, it incurs a high risk of developing into permanent hypertension over a very short period of time. These results, published in the Journal of Hypertension, outline the importance of blood pressure self-measurement by elderly persons in order to prevent the risks of heart disease and stroke.

automesure de la tension artérielle

Photo : ©Fotolia

Hypertension increases with age and is one of the major risk factors of heart disease and stroke. Since electronic devices have become available to allow people to measure their own blood pressure at home, a new type of hypertension, called masked hypertension, has been discovered. With this disorder, a person’s blood pressure is normal when measured by the doctor, but is high when measured at home. A hitherto unknown phenomenon, masked hypertension, seems to be as dangerous, if not more dangerous than classic hypertension where cardiovascular risk factors are concerned.

Based on these findings, the Inserm unit 708 “Neuroepidemiology” (University of Bordeaux Segalen, Bordeaux) worked jointly with hypertension specialists to study self-measurement of blood pressure in elderly persons who were part of the 3C cohort in Dijon. The main goal of this study was to assess the frequency of masked hypertension in a population of 1481 persons aged between 73 and 97 (average age 78.7 years). After having their blood pressure measured in an examination centre, the participants measured their own blood pressures over the next 15 days using an electronic device. The protocol consisted in recording 18 measurements over 3 days. The same measurements were taken one year later in order to assess the risk of developing permanent hypertension (high blood pressure both at home and at the examination centre).

The study revealed that masked hypertension was indeed very frequent: 40% of participants whose blood pressures were normal at the examination centre showed hypertension at home.

The researchers then analysed the development of masked hypertension, first regardless of whether the persons in the group were under treatment for hypertension or not, then in the group of persons who were not taking hypertension treatment. In the first group, the risk of developing permanent hypertension after one year was 7 times greater. In the group who initially were not under treatment for hypertension, the risk of developing permanent hypertension was multiplied by 17.

“These results outline the importance for elderly people of measuring their own blood pressure at home, in order to help diagnose masked hypertension that by definition remains undetected by the doctor, and to take measures to lower the blood pressure and thus reduce the risk of heart disease and strokes. Self-measurement of blood pressure also makes the dialogue easier between patient and doctor and helps to find a more suitable treatmentconcluded Professor Christophe Tzourio, Research Director of the Inserm unit 708

This study was financed by INPES (the French national institute for prevention and health education).

André Syrota reappointed as Inserm Chairman and CEO

André Syrota has been reappointed by the French government as Chairman and CEO of the National Institute of Health and Medical Research (Inserm), on the recommendation of the Minister for Higher Education and Research, Geneviève Fioraso.

First appointed as Inserm CEO in October 2007, Professor Syrota has been in post as Inserm Chairman and CEO since 2009. He also chairs the French National Alliance for Life and Health Sciences (Aviesan). 

portrait officiel André Syrota
© A Marouani/Inserm

A former Hôpitaux de Paris intern and a medical doctor specializing in nuclear medecine, André Syrota was born in 1946. He is a University Professor and a hospital practitioner at the Université Paris Sud. He was head of department at the CEA Hospitalier Frédéric Joliot in Orsay, and taught biophysics and nuclear medecine at the Paris Sud Faculty of Medicine. Director of Life Sciences at CEA from 1993, Pr. André Syrota was appointed Inserm CEO in October 2007.  He has held the position of Inserm Chairman and CEO since March 2009.

André Syrota is a professor of medicine and a researcher specializing in developing non-invasive functional imaging methods, based on positron emission tomography and nuclear magnetic resonance.

From his first days in office in 2007, André Syrota’s priority has been to forge partnerships with all research organisations and to foster scientific coordination at a national level: a complex task, particularly during crises such as BSE and chikungunya fever. As part of this commitment, Pr. André Syrota was the driving force behind the creation in 2009 of the French National Alliance for Life and Health Sciences (Aviesan) by the main French research organisations, thus ensuring the strategic and programmatic coordination of research into life sciences and health at a national level. Since its creation, Aviesan has set the objectives of enhancing research potential, increasing research visibility on both a national (particularly in terms of industrial players from the health sector) and international level, and ensuring research is more reactive to the emergence of fundamental scientific issues and major public health problems.

At a European level, since October 2011 Pr. André Syrota has also served as Vice-Chairman of Science Europe, an association that brings together 50 funding agencies and research organisations from 23 European countries, all working to promote the European Research Area. Within this framework, Inserm is one of the French organisations awarded the most ERC grants, for both its junior and senior researchers.

At an international level, Inserm has successfully developed a network of associate laboratories in each continent. In this way, in just a few years, Inserm has become the leading European biomedical research organisation. Its influence is apparent from the clear increase in the number of its publications featured in reviews at a national level (42% for fundamental research and 52% in specific fields).

Treatment with HDL cholesterol to aid thrombolysis

Discovery in the rat reduces bleeding complications by 90% in the only treatment available for embolic stroke

Research performed by the Neurology Department and Stroke Reception and Treatment Unit at the Bichat Hospital (AP-HP/ Paris University Diderot) and the associated INSERM Unit 698 (Prof. Amarenco, Dr Olivier Meilhac) has highlighted the benefits of good cholesterol in reducing bleeding complications in the only treatment available for embolic stroke. The results of this experiment, performed on the rat, have just been published in Stroke .

As the third cause of death in France and throughout the world and the leading cause of disability acquired in adulthood, stroke currently affects 10 million people annually, 150,000 of them in France.

To date, the treatment of reference for stroke caused by occlusion of a cerebral artery that is recognised by the ANSM consists in performing an intravenous injection (in the crook of the elbow) of a medication known as Actilyse® (alteplase) the purpose of which is to dissolve the clot. This makes it possible to cure the patient in 40% of cases, but only if the injection is started within four and a half hours of the first stroke symptoms. An unfortunate complication of the intravenous injection of this medication, however, is a brain haemorrhage with neurological deterioration that leads to death in 6% of cases, though without visible neurological deterioration in 20% of cases.

Researchers have discovered a new treatment that may reduce the risk of the bleeding complication caused by alteplase by as much as 90%. The treatment consists of high-density lipoproteins  (HDL or “good cholesterol”), isolated from human plasma. HDLs are the particles whose job it is to evacuate the bad cholesterol from inside the arteries and send it to the liver, where it is eliminated. They have other favourable actions, in that they are anti-inflammatory, anti-oxidant and anti-protease, preventing the infiltration of white blood cells into the affected area.

The team has produced a hypothesis that, through the protective effect of the blood-brain barrier[1]1, HDL can protect against the bleeding complications caused by alteplase. The team injected rats with alteplase three hours after blocking a brain artery using a filament or a clot. Bleeding occurred in 62% of the rats after the filament was withdrawn and in 46% of rats in which the brain artery was blocked by a clot. In both cases, when alteplase was injected jointly with HDLs, less than 90% fewer bleeding complications were observed. Both these models (occlusion using a filament or the creation of a clot) were used to check the effect of the treatment. The fact that the same type of result was obtained reinforces the evidence of the effect of HDLs.

This discovery, if confirmed in humans through the clinical trial we intend to perform, could revolutionise stroke treatment and offer new opportunities for improving the cure for embolic stroke victims. It is even imaginable that in future, HDL-like particles could be produced through genetic engineering”, states Professor Amarenco, Head of the Neurology Department, Stroke Reception and Treatment Unit at theBichatHospital (AP-HP/University ofParis Diderot) and co-director with Professor Steg of the “Clinical Research into Atherothrombosis” Research Team at the Mixed INSERM-University of Paris Diderot Unit 698.

These studies were partly financed by the INSERM Unit 698 and partly by the Association SOS-Attaque Cerebrale, a stroke charity.

accident vasculaire cérébral

© S Dehaenne/Inserm


[1] the nutrients supplied by the blood need to pass through it to feed the brain.

See Protective effect of high-density lipoprotein-based therapy in a model of embolic stroke.

By the sixth month of pregnancy, the human brain is capable of processing speech

A discovery by INSERM Unit U1105 “Groupe de Recherche sur l’Analyse Multimodale de la Fonction Cérébrale” [Research Group for Analysis of the Multimodal Cerebral Function] of the University of Picardy Jules Verne (UPJV) and INSERM Research Unit U992 “Neuroimagerie cognitive” [Cognitive neuroimagery], NeuroSpin/CEA

The immature brain of a premature infant is capable, at the age of three months pre-term, of distinguishing syllables uttered by male and female voices. These results obtained by INSERM researchers at the University of Picardy Jules Verne and the CEA’s NeuroSpin Imaging Centre, were published in the PNAS journal dated 25 February 2013. They highlight the very early sophisticated organisation of the regions of the brain involved in language-processing and social communication in humans.

At birth, infants are capable of distinguishing between similar syllables, of recognising their mother’s voice and of differentiating between several human languages. Are these abilities in the human infant due to the presence of innate mechanisms specific to the human race for processing speech or do they indicate swift learning of the characteristics of the mother’s voice during the final weeks of pregnancy?

To discover the truth, Fabrice Wallois, Director of the mixed UPJV/INSERM research unit known as the “Research Group for Analysis of the Multimodal Cerebral Function” (GRAMFC), and Ghislaine Dehaene-Lambertz, (INSERM, NeuroSpin/Atomic Energy and Alternative Energies Commission (CEA), University of Paris-Sud) in collaboration with hospital doctors at the Amiens Picardy University Hospital, tested the auditory discrimination abilities of twelve premature babies, born at 28 to 32 weeks of amenhorræa, i.e. born two to three months’ pre-term.

At this stage of development, the brain is immature since the neurones are still in the process of migrating to their final destination. Yet the first connections between the brain and the outside world are being set up, especially those that enable the fœtus to hear sounds, thus enabling it to record the first brain responses to external stimulation.

The authors of this study stimulated premature infants by using audio stimulation, exposing them to the sounds of two similar syllables (“ga” and “ba”) pronounced by either a man or a woman. They recorded the brain responses by using functional optical imaging (near infrared spectroscopy (NIS)). The researchers were thus able to show that despite the fact that their brains were still immature, the premature babies were receptive to changes in the voice (male or female) and changes in phonemes ( “ba” or “ga”) (figure 1).

Furthermore the sets or networks of neurones involved in premature babies are very similar to those described in the adult when performing the same type of task. They are asymmetrical and especially involve the frontal areas. As in adults, the right frontal area responds to newness, regardless of the change involved, whereas the left frontal area or Broca’s region, only responds to a change of phoneme.

Figure 1: Projection of brain activation in a premature baby born at 30 weeks of amenorrhæa. The change of phoneme produces an increase in brain activity in the temporal and frontal areas, especially the left. The response to a change in the voice is more limited and only involves the change of voice is more limited, and only involves the lower right frontal area.

©Wallois

These results show very early, as soon as the first cerebral connections are established (three months before term) and above all before any learning process has occurred, that the human brain is capable of processing special characteristics of human speech thanks to the sophisticated organisation of certain language areas of the brain (the right and left perisylvian regions). Since the organisation of the regions of the brain being governed by genetic expression during the development of the fœtus, the authors suggest that the emergence of language is largely influenced by genetics and thus by innate mechanisms.

This study received support from the Picard Regional Council and the ERDF (European Regional Development Fund). 

 

 

COMBACTE: A new step in the fight against resistance to antibiotics

Antimicrobial resistance represents is a growing problem in public health due the increasing rarity of antibiotics capable of combating resistant bacteria. The COMBACTE project, that has just obtained 195 million euros worth of finance from the Innovative Medicines Initiative (IMI), aims to work to develop new antibiotics and introduce a successful clinical trials platform combining private and public research. 

Developing innovative clinical trials for antibiotics

The COMBACTE (Combatting Bacterial Resistance in Europe) project, resulting from the sixth Call for proposals issued by the IMI, is one of the projects that is part of the “New Drugs For Bad Bugs” (ND4BB) programme. It is the result of the initial association between industry and two academic consortia, the Eu-ACT and INCRAID, run respectively by Marc Bonten of the University of Utrecht and Bruno François of Limoges University Hospital, both being responsible for overall project coordination along with representatives of the EFPIA, Scott White (GlaxoSmithKline) and Seamus O’Brien (Astra Zeneca).

The project will last for seven years and will bring together about 20 partners from all overEurope. It is designed to generate innovative trials to facilitate the registration of new anti-bacterial agents, mainly through the creation of a network of experienced investigators. It will also design and validate tests to support the diagnosis of patients, identify the most suitable treatments and monitor the treatment response.

Much of the project will be devoted to performing clinical trials of anti-infectious medication currently being developed by the pharmaceutical companies involved in the programme. The first antibiotic to be subjected to clinical trials under the COMBACTE programme has been developed by GlaxoSmithKline’s laboratories.

For these purposes, the total budget for the COMBACTE project amounts to nearly 195 million euros, a scale of finance hitherto unequalled in private-public clinical research.

French partners in the European COMBACTE Project

Of the various partners, several French entities are involved in the COMBACTE project.

Dr Bruno François, under the aegis of Limoges University Hospital, will be responsible for coordinating the clinical trials in collaboration with all the European investigator centres and the GSK Group and GSK France (GSK Medical Management France) Research Groups. Dr François will also participate in the overall project management.

INSERM and its Midi-Pyrénées/Limousin directorate headed by Armelle Barelli will be responsible for budget management for all the project’s clinical trials.

ECRIN (European Clinical Research Infrastructures Network) coordinated by INSERM and headed by Professor Jacques Demotes, is an infrastructure whose purpose is to facilitate the setting up of international trials in Europe. ECRIN will be responsible for the management of the project’s clinical trials through its European partners, ensuring coordination between the various national networks.

Dr Laurent Abel (INSERM U980 “Human genetics of infectious diseases”), another French member of the consortium, will participate in the identification in humans of genetic markers affecting the  susceptibility/resistance to bacterial infection and the response to their treatment, along with the other  partners.

Two French networks will also participate in clinical trials  for the COMBACTE project, the Réseau National de Recherche Clinique en Infectiologie (RENARCI) coordinated by Professor Bruno Hoen (Besançon University Hospital), with the support of the Institut Thématique Multi-Organismes “Microbiologie et Maladies Infectieuses” (IMMI) directed by Professor Jean-François Delfraissy, and the CRICS (Clinical Research in Intensive Care and Sepsis) network, headed by Dr Bruno François and Professor Pierre-François Dequin at the Tours University Hospital.  The Groupe pour la Recherche et l’Enseignement en Pneumo-Infectiologie (a Working Party emanating from the Société de Pneumologie de Langue Française) coordinated by Professor Anne Bergeron at the AP-HP Saint-Louis with the collaboration of Dr Muriel Fartoukh at the APHP Tenon will be associated with the CRICS network.

COMBACTE, a unique excellence project with international visibility

COMBACTE is the European public/private partnership set up for the development of drugs.

The development of new antibiotics represents a challenge that justifies the association of several of the major players. By bringing together experts in the various fields (research bodies, universities, hospitals and the pharmaceutical industries) specialising in microbiology, epidemiology, the development of drugs and clinical trials, the aim of COMBACTE is to improve and accelerate the development of antibiotics.

Unique in its scale, ambitious, with benefits that can be expected for patients, public health and research in Europe, COMBACTE has the potential to become the leading light in Europe in the antimicrobial drug development.

The fight against anti-microbial resistance –  the “New Drugs For Bad Bugs” programme

Antimicrobial resistance represents a serious and growing world threat to human and animal health. According to the World Health Organization, “resistance to antibiotics is about to become a public health emergency of yet unknown proportions”. In Europe, resistance to antibiotics is responsible for more than 25,000 deaths annually and the cost of treatment is estimated at 1.5 billion euros annually. New forms of resistance emerge every day, leaving clinicians increasingly devoid of solutions to fight infections. Despite the recognised need to develop new antibiotic weapons, only two new classes of medication have entered the market in the last thirty years.

In November 2011, the European Commission, as part of its Action Plan to combat the increasing threat of antimicrobial resistance, called for “unprecedented collaborate research and development effort to bring new antibiotics to patients” including the launch of the sixth IMI Call for proposals in May 2012 as part of the programme entitled “ New Drugs For Bad Bugs”.

IMI : a unique public-private partnership programme

IMI (Innovative Medicines Initiative) is a unique European public-private partnership between the European Commission and the EFPIA (European Federation of Pharmaceutical Industries and Associations), each contributing one billion euros to finance various projects through issuing tenders.

The aim of the IMI is to propose a coordinated approach to promote the development of safer and more effective treatments for patients by encouraging collaboration between various academic and industrial partners, the public authorities and patient associations and by increasing European competitiveness.

The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under Grant Agreement n°115523, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.

L’Inserm et l’Université Toulouse III – Paul Sabatier renouvellent leur partenariat

L’Inserm et l’Université Toulouse III – Paul Sabatier renouvellent leur partenariat en matière de recherche, de valorisation et de transfert de connaissances en sciences du vivant. 

Se fondant sur les actions et les résultats de la convention précédente, les deux partenaires fixent les modalités de leur collaboration pour les trois  prochaines années.

Le Professeur André Syrota, Président-directeur général de l’Inserm, Bertrand Monthubert, Président de l’Université Toulouse III – Paul Sabatier ont signé le 18 janvier dernier une convention de mixité qui inscrit dans la dynamique leur partenariat pour la conduite des recherches communes. Elle prévoit les modalités de gestion des unités de recherche d’une part et celles de la valorisation des travaux de recherche qui en sont issus d’autre part.  

Dans le contexte des principes définis dans l’accord-cadre du 16 novembre 1998, l’Université Toulouse III – Paul Sabatier et l’Inserm conviennent d’assurer le développement scientifique des unités de recherche communes Inserm/ Université Toulouse III – Paul Sabatier. Pour ces unités existantes ou futures, l’Inserm et l’Université Paul Sabatier s’engagent ainsi à développer les moyens nécessaires afin de :

  • assurer une production scientifique de haut niveau et une continuité entre la recherche biologique et biomédicale cognitive et la recherche médicale, clinique et en santé publique ;
  • veiller à la complémentarité des activités de formation et de recherche et contribuer à la qualité de la formation des étudiants à la recherche et par la recherche ;
  • favoriser la mutualisation des moyens, le développement de plateaux techniques et à la collaboration pour la recherche en sciences de la vie et de la santé ;
  • et enfin développer ensemble des activités de transfert et de valorisation.

Cette convention concerne 7 unités mixtes de recherche et 2 unités mixtes de service, dans lesquelles travaillent plus de 900 personnels (dont 650 chercheurs et enseignants-chercheurs).

De nombreux projets scientifiques au rayonnement international sont portés par ce partenariat entre l’Inserm et l’Université Toulouse III – Paul Sabatier, comme par exemple les implantations du Centre de recherche en cancérologie de Toulouse (CRCT) ou de Stromalab (en partenariat avec l’EFS et le CNRS) au sein de l’Oncopole. L’Europe vient également reconnaître nos équipes mixtes avec un projet porté par Nathalie Vergnolle (CPTP) labellisé par l’ERC.

Plusieurs prix scientifiques de haut niveau récompensent régulièrement les recherches menées dans ces laboratoires : Philippe Le Bouteiller du CPTP, lauréat de l’Académie nationale de médecine ou Alicia Mallet, doctorante à l’UDEAR et lauréate d’un prix de la Fondation pour la recherche médicale.

En matière de valorisation, cet accord reconduit les termes de la démarche partenariale engagée par les deux institutions pour protéger et valoriser les résultats obtenus dans les Unités Mixtes de Recherche Inserm-UPS.

Pour chacune des unités mixtes de recherche afin d’optimiser l’accompagnement des chercheurs dans leur démarche de valorisation, l’Inserm et l’UPS ont ainsi décidé de désigner un maître d’œuvre unique et de le doter d’un mandat d’action étendu ; respectivement Inserm Transfert pour les unités dont la valorisation est attribuée à l’Inserm, et Toulouse Tech Transfer pour les unités dont la valorisation est attribuée à l’Université.

Le maître d’œuvre unique assure la protection des résultats de recherche et leur valorisation, jusqu’à la signature de contrats de recherche collaborative ou de cession de licence. Les revenus d’exploitation sont répartis à parts égales entre les deux institutions. En outre, Inserm Transfert et Toulouse Tech Transfer travailleront en étroite collaboration sur les dossiers nécessitant un financement en maturation ; l’enveloppe dédiée à l’accompagnement de projets émanant des UMR en phase précoce de transfert étant également reconduite.

Les unités mixtes Inserm / UPS en Midi-Pyrénées

Imagerie cérébrale et handicap neurologique (Inserm – UPS)

  • Epidémiologie et analyses en santé publique (Inserm – UPS)
  • Stromalab (CNRS – UPS – Inserm – Établissement français du sang)
  • Centre de recherche en cancérologie de Toulouse (Inserm – UPS, ERL CNRS)
  • Centre de physiopathologie de Toulouse Purpan (Inserm – UPS – CNRS – USC INRA)
  • Institut des maladies métaboliques et cardiovasculaires (Inserm – UPS)
  • Unité de différenciation épidermique et autoimmunité rhumatoïde (CNRS – UPS – Inserm)
  • Centre Régional d’Exploration Fonctionnelle et de Ressources Expérimentales CREFRE – Anexplo (Inserm – UPS)
  • French Clinical Research Infrastructure Network – F-CRIN (Inserm – UPS – CHU Toulouse)
A propos de l’Inserm

L’Inserm est le seul organisme public français entièrement dédié à la recherche biologique, médicale et en santé des populations. L’Inserm mène une recherche par essence multithématique. Elle permet l’étude de toutes les maladies, des plus fréquentes aux plus rares. L’Inserm se positionne sur l’ensemble du parcours allant du laboratoire de recherche au lit du patient. Depuis janvier 2008, l’Inserm s’est vu confier une mission de coordination de la recherche biomédicale française, et pour assurer celle-ci, il s’est engagé dans une réforme fonctionnelle, concrétisée par la création de huit instituts thématiques. En savoir plus >> http://www.inserm.fr

A propos de l’Université Toulouse III – Paul Sabatier

Dans un souci constant de mieux insérer ses étudiants, l’Université Paul Sabatier a développé depuis plus de trois décennies ses relations partenariales avec le secteur socio-économique. L’UPS a été une des premières universités en France reconnue pour la qualité de sa valorisation par l’attribution d’un programme multi-formations. La création en 2010 de la division du partenariat et de la valorisation, au sein de la Direction du Soutien aux laboratoires devrait encore renforcer la professionnalisation de cette activité au service de tous les acteurs de l’université. En savoir plus >> www.univ-tlse3.fr

Obesity and insulin resistance: the lipolysis route

Photo : ©Fotolia

Liver and skeletal muscle resistance to the action of insulin is an early sign of the development of Type 2 Diabetes. The INSERM team at the “Obesity Research Laboratory ” in the Institut des Maladies Métaboliques and Cardiovasculaires (INSERM / Université Toulouse III – Paul Sabatier), headed by Dominique Langin, has shown through results published this week, that there is an association between lipolysis (mobilisation of fat in response to the body’s need for energy) and insulin sensitivity in humans. Researchers also showed that a reduction in lipolysis in mice, through genetic modification or pharmacological treatment, improved the action of insulin on glucose metabolism in the liver and the muscles. Lipolysis inhibition could be used in treating insulin resistance in the obese.

The results are accessible on the website of the Plos Biology journal for 19 February 2013.

Insulin is the hormone that controls the blood glucose level, inhibiting its production by the liver and stimulating its use in the muscles. When the body needs energy, during fasting or due to physical exercise, the triglycerides stored in the adipose tissue are released in the form of fatty acids through the action of adipocyte lipolysis. When this happens, the fatty acids have a favourable action because they are supplying energy.

These fatty acids may also have a deleterious action, however. When they are present in excessive quantities, as in the case of obesity, they are deposited in the peripheral organs and interfere with the action of insulin. Other lipids and proteins produced by an excess of adipose tissue are also involved in the development of insulin resistance. (Figure 1 opposite)

Figure 1 : Excess of fat mass and insulin resistance

© INSERM / Dominique Langin

Professeur Langin’s team at the Institut des Maladies Métaboliques and Cardiovasculaires (I2MC, Toulouse), (INSERM, Université Toulouse III – Paul Sabatier, Hôpitaux de Toulouse), in collaboration with other I2MC teams and researchers in Sweden at the Karolinska Institutet in Stockholm and Lund University, are seeking ways to treat insulin resistance, using a treatment strategy that avoids the onset of diabetes in the obese.

In this study, they showed that a reduction in adipocyte lipolysis through genetic modification or pharmacological treatment improves insulin sensitivity. An exploration of the mechanisms involved showed that the reduction in lipolysis causes a reduction in the flow of fatty acids within the organism and is accompanied by an improvement in insulin action on glucose metabolism in the liver and muscles.

“We discovered the effects of lipolysis reduction in humans through analysing data from cohorts of obese people in whom we reported that a reduction in lipolysis was associated with an improvement in insulin sensitivity. These results are all the more interesting in that they introduce a treatment strategy in which lipolysis inhibition does not involve any change to body weight”, explains Dominique Langin.

This study also showed quite unexpectedly that when lipolysis was reduced in mice, a special metabolic pathway, known as de novo lipogenesis, was activated enabling the synthesis of fatty acids directly from glucose (Figure 2 below). In Spring, 2012, a team from Harvard University, United States, suggested that the activation of de novo lipogenesis in adipose cells reduced resistance to the action of insulin. A clinical trial performed by Professor Langin’s team at the Centre d’Investigation Clinique INSERM-CHU de Toulouse also shows that chronic treatment with an anti-lipolytic molecule induced an increase in the expression of de novo lipogenesis genes in the adipocyte.

Figure 2 : Inhibition of the mobilisation of fat (lipolysis)  through the adipose cell reduces insulin resistance by increasing lipogenesis de novo.

© INSERM / Dominique Langin

Researchers are now attempting to identify the mediators produced by the adipose cell participating in the improvement of insulin action, as well as demonstrating the important of this treatment strategy in pre-diabetic obese patients.

(French) Infection VIH par voie sexuelle : élucidation de mécanismes-clé chez l’homme

The HOMAGE (Heart OMics in AGEing) project, coordinated by the French National Institute of Health and Medical Research (INSERM), has been awarded a grant by the European Commission for a 6 year period. The project aims to identify and validate specific biomarkers of heart failure in order to prevent the development of the disease affecting elderly population. 17 research groups from 10 countries will collaborate to investigate new ways of preventing heart failure. The project will use an innovative ‘omic-based’ approach which investigating simultaneously a huge amount of genes, proteins and metabolites.

The 17 partners will meet at Nancy on February 22nd for the kick off meeting of HOMAGE.

Professor Faiez Zannad, Head of the Centre d’Investigation Clinique Pierre Drouin Inserm U9501 and Inserm Unit 1116 based in Nancy, is the project coordinator.  The 12 million euros grant of the European Commission will be dedicated to the HOMAGE consortium for research on heart failure, a serious illness altering myocardial activity which affects more than 6.5 million persons in Europe. Indeed, the prevalence of heart failure is increasing worldwide due to an ageing population as well as a rising trend of risk factors for heart disease such as diabetes, obesity and hypertension.

Heart failure is a major cause of mortality and morbidity in the world and remains the most frequent cause of hospitalization for patients over 65 years old.

The costs related to heart failure have been estimated around 1.5 billion euros per year in France[1].

Photo : ©Serimedis/Inserm

Despite important progress in the treatment including new drugs, new medical devices and innovative disease management programmes, the diagnosis of heart failure is often difficult in older adults with co-morbidities. Screening tests are usually based on blood pressure, glycaemic and cholesterol control. Although they are useful to detect high risk patients, they are limited regarding their sensitivity and specificity. During the past decade, promising biomarkers such as natriuretic peptides have been identified to diagnose heart failure, but their predictive value remains relatively poor. The HOMAGE consortium is willing to validate more specific and more sensitive biomarkers which should facilitate an early detection of the disease in patients at risk.

To achieve this goal, the consortium agreed on the use of an ‘omic-based’ approach. This approach aims to validate promising biomarker candidates by crossing a large volume of data (genomics, proteomics, miRNomics, transcriptomics and metabolomics). This would permit scientists to understand new pathophysiological mechanisms, signaling pathways and identify new therapeutic targets to prevent heart failure.

The HOMAGE consortium will manage cohorts for a total of 30 000 patients. The European researchers will firstly identify biomarker candidates in blood and study their predictive value for heart failure and common co-morbidities associated with ageing (renal impairment, cognitive disorders…). Subsequently, HOMAGE will lead a clinical trial to look for novel treatments of heart failure that can be targeted specifically to those patients at risk.

This trial will allow identifying patients’ omics based biomarker profiles most likely to predict response to treatment with the better benefit/risk ratio, an attempt into personalized medicine.


[1] Fédération Française de Cardiologie

The 17 partners of HOMAGE project : www.homage-hf.eu (en ligne le 21 février)

Inserm, France : http://www.inserm.fr/

Inserm U942/ Biomarqueurs et maladies cardiaques, France

Inserm UMR 1048/ Equipe 7, France

Inserm U744/ Recherche des Déterminants Moléculaires des Maladies Cardiovasculaires, France

Inserm Transfert, France : http://www.inserm-transfert.fr/

European Drug Development Hub, France : http://www.fondationtransplantation.org

ACS Biomarker, Pays-Bas : http://acsbiomarker.com/

Randox Testing Service, Royaume-Uni : http://www.randoxtestingservices.com/

Medical University of Graz, Autriche : http://www.meduni-graz.at/en/

University of Manchester, Royaume-Uni : www.manchester.ac.uk

Fundación para la Investigación Médica Aplicada, Espagne : www.cima.es

University College Dublin, Irlande : www.ucd.ie

University of Hull, Royaume-Uni : www.hull.ac.uk

Maastricht University, Pays-Bas : http://www.maastrichtuniversity.nl/

Istituto di Ricerche Farmacologiche ‘Mario Negri’, Italie : http://www.marionegri.it/mn/en/

Hannover Medical School, Allemagne : http://www.mh-hannover.de

University of Leuven, Belgique : www.kuleuven.be/english/

London School of Hygiene, Royaume-Uni : http://www.lshtm.ac.uk/

Emory University, Etats Unis : http://www.emory.edu

University of Glasgow, Royaume-Uni : http://www.gla.ac.uk/

Collaborative institutions:

The Trustees of Boston University, National Heart, Lung, and Blood Institute’s Framingham Heart Study, Etats Unis

Imperial College, Royaume-Uni

Steno Diabetes Center (Novo Nordisk), Danemark

HOMAGE – Overcoming Heart Failure, an European challenge

The HOMAGE (Heart OMics in AGEing) project, coordinated by the French National Institute of Health and Medical Research (INSERM), has been awarded a grant by the European Commission for a 6 year period. The project aims to identify and validate specific biomarkers of heart failure in order to prevent the development of the disease affecting elderly population. 17 research groups from 10 countries will collaborate to investigate new ways of preventing heart failure. The project will use an innovative ‘omic-based’ approach which investigating simultaneously a huge amount of genes, proteins and metabolites.

The 17 partners will meet at Nancy on February 22nd for the kick off meeting of HOMAGE.

Professor Faiez Zannad, Head of the Centre d’Investigation Clinique Pierre Drouin Inserm U9501 and Inserm Unit 1116 based in Nancy, is the project coordinator.  The 12 million euros grant of the European Commission will be dedicated to the HOMAGE consortium for research on heart failure, a serious illness altering myocardial activity which affects more than 6.5 million persons in Europe. Indeed, the prevalence of heart failure is increasing worldwide due to an ageing population as well as a rising trend of risk factors for heart disease such as diabetes, obesity and hypertension.

Heart failure is a major cause of mortality and morbidity in the world and remains the most frequent cause of hospitalization for patients over 65 years old.

The costs related to heart failure have been estimated around 1.5 billion euros per year in France[1].

Photo : ©Serimedis/Inserm

Despite important progress in the treatment including new drugs, new medical devices and innovative disease management programmes, the diagnosis of heart failure is often difficult in older adults with co-morbidities. Screening tests are usually based on blood pressure, glycaemic and cholesterol control. Although they are useful to detect high risk patients, they are limited regarding their sensitivity and specificity. During the past decade, promising biomarkers such as natriuretic peptides have been identified to diagnose heart failure, but their predictive value remains relatively poor. The HOMAGE consortium is willing to validate more specific and more sensitive biomarkers which should facilitate an early detection of the disease in patients at risk.

To achieve this goal, the consortium agreed on the use of an ‘omic-based’ approach. This approach aims to validate promising biomarker candidates by crossing a large volume of data (genomics, proteomics, miRNomics, transcriptomics and metabolomics). This would permit scientists to understand new pathophysiological mechanisms, signaling pathways and identify new therapeutic targets to prevent heart failure.

The HOMAGE consortium will manage cohorts for a total of 30 000 patients. The European researchers will firstly identify biomarker candidates in blood and study their predictive value for heart failure and common co-morbidities associated with ageing (renal impairment, cognitive disorders…). Subsequently, HOMAGE will lead a clinical trial to look for novel treatments of heart failure that can be targeted specifically to those patients at risk.

This trial will allow identifying patients’ omics based biomarker profiles most likely to predict response to treatment with the better benefit/risk ratio, an attempt into personalized medicine.


[1] Fédération Française de Cardiologie

The 17 partners of HOMAGE project : www.homage-hf.eu (en ligne le 21 février)

Inserm, France : http://www.inserm.fr/

Inserm U942/ Biomarqueurs et maladies cardiaques, France

Inserm UMR 1048/ Equipe 7, France

Inserm U744/ Recherche des Déterminants Moléculaires des Maladies Cardiovasculaires, France

Inserm Transfert, France : http://www.inserm-transfert.fr/

European Drug Development Hub, France : http://www.fondationtransplantation.org

ACS Biomarker, Pays-Bas : http://acsbiomarker.com/

Randox Testing Service, Royaume-Uni : http://www.randoxtestingservices.com/

Medical University of Graz, Autriche : http://www.meduni-graz.at/en/

University of Manchester, Royaume-Uni : www.manchester.ac.uk

Fundación para la Investigación Médica Aplicada, Espagne : www.cima.es

University College Dublin, Irlande : www.ucd.ie

University of Hull, Royaume-Uni : www.hull.ac.uk

Maastricht University, Pays-Bas : http://www.maastrichtuniversity.nl/

Istituto di Ricerche Farmacologiche ‘Mario Negri’, Italie : http://www.marionegri.it/mn/en/

Hannover Medical School, Allemagne : http://www.mh-hannover.de

University of Leuven, Belgique : www.kuleuven.be/english/

London School of Hygiene, Royaume-Uni : http://www.lshtm.ac.uk/

Emory University, Etats Unis : http://www.emory.edu

University of Glasgow, Royaume-Uni : http://www.gla.ac.uk/

Collaborative institutions:

The Trustees of Boston University, National Heart, Lung, and Blood Institute’s Framingham Heart Study, Etats Unis

Imperial College, Royaume-Uni

Steno Diabetes Center (Novo Nordisk), Danemark

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