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Month: March 2013

Hervé Chneiweiss appointed Head of Inserm’s Ethics Committee

Posted on by Priscille Rivière

Hervé Chneiweiss, a research director at the CNRS, has just been appointed President of the Inserm Ethics Committee. Inserm’s Ethics Committee for medical research and health was set up in 2000 with the aim of playing an active part in the dialogue between Society and the scientific and medical communities. He takes over from Jean-Claude Ameisen, the President of the French National Consultative Ethics Committee (CCNE). 

Hervé Chneiweiss

Copyright : Pierre Malaval

Hervé Chneiweiss, medical doctor and scientist, neurologist and neurobiologist, has always integrated the ethical questions posed by progress and research into his clinical and scientific work. From 2000 to 2002, he was a technical consultant for life sciences and bioethics at the Ministry of Research. He has been a member of the Inserm Ethics Committee since 2003 and has contributed to numerous articles published in international scientific reviews and works on bioethics.

He will be President of the Ethics Committee, whose work is to discuss and develop reflection on ethical aspects of practices used for biomedical research; to keep watch and advise in order to prepare the conditions for innovatory research and ensure that all practices are accompanied by ethical principles, particularly as concerns their impacts and consequences; to ensure awareness and guidance in ethical questions and to play a full part in communication between the scientific and medical community, Inserm and Society.

Hervé Chneiweiss is delighted with this

“rewarding mission to create the conditions required for ongoing ethical awareness and discussion within Inserm and to contribute to interfaces between the decision-makers and Society”.

“For Inserm, more than any other institution, it is an absolute necessity to be able to reply to ethical questions posed both by researchers and by all of our fellow citizens. I am delighted that Hervé Chneiweiss has accepted this complex task; we all know the extent to which his ideas have enriched ethical thinking”,

 states André Syrota, Chief Director and President of Inserm.

Hervé Chneiweiss is also Research Director of the “Glial plasticity and brain tumors” research team and is Director of the Paris-Seine Neurosciences Laboratory (Inserm/CNRS/UPMC) at the new Paris-Seine Institute of Biology, that groups together the biology laboratories from the Jussieu campus.

He is working on the biology of a specific population of cells from the nervous system, known as astrocytes. Astrocytes make up half of all brain cells and fulfill numerous functions, from constructing the architecture of the brain to being involved in each phase of communication between neurons. Hervé’s team are making a specific study into the mechanisms that link astyrocytes to the cause and development of brain tumors. By characterizing stem cells within brain tumors, it could be possible to develop new therapeutic strategies to fight cancer.

Editor of the review Médecine/Sciences since 2006, Hervé Chneiweiss is also a member of the Scientific Council of the Parliamentary Office of Scientific and Technological Assessment (OPECST), member of the Scientific Council of the French Foundation for Medical Research (FRM) and of the Institute of Biological Sciences at the CNRS.

He is also co-author of “Bioéthique: Avis de tempêtes” (with Jean-Yves Nau, Alvik, 2003), and author of “Neuroscience et Neuroéthique : des cerveaux libres et heureux” (Alvik 2006) and “L’homme réparé” (Plon 2012).

AgedBrainSYSBIO, a research initiative against neurodegenerative diseases

Posted on by Priscille Rivière

A European group of academic laboratories and industrial scientists from SMEs will combine integrative systems biology & comparative genomics for studying human brain ageing and/or most common age-related diseases with a special emphasis on late-onset Alzheimer Disease for identifying and validating new molecular targets and biomarkers. This four-year research programme is coordinated by Inserm (Pr Michel Simonneau).

March 19 2013 – The AgedBrainSYSBIO project on systems biology of synapse proteins & ageing was officially launched March18th in Paris, France. AgedBrainSYSBIO is a European collaborative research project funded by the European Commission under the Health Work Programme of the 7th Framework Programme. This multidisciplinary consortium assembles 14 academic and industrial internationally renowned research teams from Belgium, Estonia, France, Germany, Israel, United Kingdom and Switzerland.

Ageing is undisputedly a complex process because it affects the deterioration of most (if not all) aspects of life. Cognitive decline is emerging as one of the greatest public health challenges of the old age, with nearly 50% of adults over 85 afflicted by Alzheimer’s disease, the most common type of dementia.
Neurone humain en culture

©E Eugène/Inserm


As other chronic and neurodegenerative diseases, Alzheimer’s disease develops slowly and gradually; but is distinctive in that it forces patients to endure many years of steadily-lessening contact with others, because of memory loss, difficulty with orientation, loss of language and speaking abilities, judging things and depression amongst numerous other symptoms. In 2013, it is estimated that there are worldly more than 24 million people with Alzheimer’s disease, with 4.6 million new cases each year, which means a new case each 7 seconds. It is thus one of the greatest challenges in public health for modern societies, in terms of costs but also in terms of cause, cure and care. To address all these issues, European Commission-funded research effort is crucial as there are still no curative drugs, with only symptomatic treatment able to delay the disease progression.

Over the last years, Genome-Wide Association Studies (GWAS) have been instrumental to identify genes that mediate genetic risk associated to Late-Onset Alzheimer Diseases (LOAD). These approaches based on the genetic comparison of large cohorts of patients and healthy aged persons, and for which three academic partners have been involved (Inserm U894; Institut Pasteur Lille, University of Antwerpen), have been largely funded by Europe. Additionally, a variety of new sets of data have been built and have delivered the state-of-the art of protein-protein interactions, their localisation in subregions of human neurons and genome-wide transcriptome analysis of human neurons derived from aged patient fibroblasts. In another field, new drosophila and mouse models have been also generated via academic partners involved in European Commission-supported large-scale programmes. Finally, the analysis of genes displaying an accelerated evolution in humans as non-human primates do not display these human-specific neurodegenerative diseases has open interesting research paths. So far however, in spite of a huge amount of data available and existing in vitro and in vivo models, these approaches have not been successfully translated into the clinic separately.

The AgedBrainSYSBIO will take advantage of these large set of data, will cross them to other large-scale ageing databases and will include all of these know-how, technologies and results. Thanks to the involvement of four European SMEs, this program is expected to get results readily translated into preclinical studies.

AgedBrainSYSBIO project assembles 13 well-established research teams both from academia and industry. The scientists will share results and know how on LOAD GWAS gene discovery, comparative functional genomics in mouse and drosophila models, in mouse transgenic approaches research on human induced pluripotent stem cells (hiPSC) and their differentiation in vitro and modelling pathways with emphasis on comparative and evolutionary aspects. Importantly, the four European SMEs involved will bring their complementary expertise. QURETEC (Estonia) will be a key partner for data management solutions and bioinformatics data analyses; HYBRIGENICS (France) is a world leader in comparative proteomics and protein-protein interaction analyses; GENEBRIDGES (Germany) is marketing novel strategies for DNA engineering in mammalian cells; reMYND (Belgium) is a leader for development of protein misfolding-modifying treatments against LOAD .

Together, researchers will address the basis of brain ageing by studying the pathways involved in Late-Onset Alzheimer Diseases combining integrative systems biology and comparative genomics. One of the first steps will be to identify the interactions through which the ageing phenotype develops in normal and in disease conditions; on this basis, novel pathways and their evolutionary properties will be modelled and experimentally tested in order to identify druggable targets. This work will finally allow the validation of new druggable targets and markers as a proof-of-concept towards the prevention and cure of aging cognitive defects.

Michel Simonneau, MD PhD, Professor at Ecole Normale Supérieure de Cachan, who coordinates this effort states that “this ambitious project integrates the numerous European initiatives, such as JPND1 , as well as national research programmes, which addresse the scientific and societal challenge of neurodegenerative diseases. This project receives the decisive input of 4 small to medium size enterprises (SMEs) that allow us to get candidate solutions for curing and preventing common age-related diseases. The links between academia and industry is the driving force of this work programme and in the end will hopefully benefit to all of us.”

The AgedBrainSYSBIO consortium is coordinated by the French National Institute for health and medical research (Inserm, Prof. Michel Simonneau) and brings together scientists with internationally recognized expertise in systems biology of the synapse and four small to medium size enterprises (SMEs) with a leading role in the project. The SME partners will assure translation of project results to clinical application.

[1] JPND,  for EU Joint Programme – Neurodegenerative Disease Research ; see http://www.neurodegenerationresearch.eu

Characterisation of the immune cells capable of controlling HIV infection

Posted on by Priscille Rivière

How is it that certain patients infected by HIV have immune cells that are capable of controlling the infection? Victor Appay, INSERM Research Director (Mixed INSERM  Research Unit 945 “ Immunity and Infection” / Université Pierre and Marie Curie / Hôpital Pitié-Salpêtrière (AP-HP)) and his colleagues have succeeded in identifying the molecular characteristics of certain T lymphocytes that have the specific property of being able to detect and control HIV and its mutant versions. Their work was published in 22 March 2013 in the Immunity journal and has received support from the ANRS. 

Today, according to the OMS, 34 million people are infected with HIV, yet only 1.3 million sufferers in the poorest countries are being treated and 6,800 people a day are infected by HIV.

The Human Immunodificiency Virus (HIV) attacks the cells of the immune system and destroys them or renders them ineffectual. Acquired Immunodeficiency Syndrome (AIDS) is the final stage in HIV infection. It may appear after 10 to 15 years.

The inherent danger in a virus lies very much in its ability to develop multiple strategies to escape detection by the immune system. HIV is no exception to the rule. HIV is known to mutate and adapt in each individual and his/her major histocompatibility complex (MHC).

HIV is a good example of how a pathogenic agent can evolve and mutate by creating what is known as a new variant, in order to circumvent its host’s immune system.

In certain cases, however, the immune system is able to react to control these mutant pathogens.

The molecular basis of the process has not been clearly established hitherto, but this is what researchers have now been able to do. Their work makes it easier to under the mutual adaptation mechanism between the immune system and HIV.

In order to better understand how HIV works, Victor Appay, INSERM Research Director, in collaboration with his colleagues at Cardiff University (United Kingdom), Kumamoto University (Japan) and Monash University (Australia), and with the support of the ANRS, studied the cells of patients whose immune response proved effective against the virus and its variants. These patients, all of them from the ANRS Primary Infection cohort, were monitored from the time primary infection with HIV was diagnosed. The detailed study focused on the response caused by the T CD8+ lymphocytes of patients infected by HIV and in whom these cells were particularly well preserved and functional.

In other words, these cells not only managed to control and reduce the replication of HIV but even of its variants, something that is not the case in patients who develop the full-blown disease.

This protective immune response is possible due to certain T CD8+ lymphocytes, that are known as “cross reactive”. They have a receptor on the surface whose structure gives then the special ability to recognise not only the non-mutant virus but even its mutant variants. This discovery is the first to really pinpoint how HIV can be controlled by certain T CD8+ lymphocytes.

The study highlights the complexity of the forces and mechanisms that lead to the development of the virus and the way it alters the immune system during the course of HIV infection. A better understanding of immunological determinants as the basis for control of replication of HIV is essential for the development of effective vaccines. In fact, the choice between immunogens and adjuvants in the development of vaccines against HIV needs to be rationalised in order to encourage the production of T CD8+ lymphocytes that are particularly skilled at recognising the wilder and mutant forms of the virus.

New reference web portal on health research in Europe

Posted on by Priscille Rivière

The EU-funded CommHERE project launches Horizonhealth.eu

The Horizon Health web portal (www.horizonhealth.eu) has been officially launched today by Professor Anne Glover, Chief Scientific Advisor, European Commission, in the presence of the communication representatives of leading research institutions in Europe. The Horizon Health web portal aims to become a valuable online resource for journalists and interested citizens looking for accurate, up-to-date, and attractive information on health research funded by the EU.

”Research not communicated is research not done,” states Professor Anne Glover.”The European Commission is supporting many forward-thinking and cutting-edge research projects that need to be shared with European citizens. The web portal set-up by the CommHERE project is an important milestone that should enable the dissemination of key health-related research results on a European level.”

Studies show that European citizens are interested in learning more about science and medical developments, directly from the researchers [Eurobarometer 2010]. The Horizon Health web portal will help mediate a dialogue: introducing leading scientists and their projects in an attractive and accessible way, and featuring striking images that convey the interest and fascination that drive the research teams. More options and functionalities, such as videos, illustrations and webinars will be added over time to enable a direct interaction and more in-depth understanding.

“The launch of HorizonHealth.eu is a crucial step forward for the CommHERE project,” explains Dr Ulla Bredberg from the Karolinska Institutet, who coordinates the project. “From working on local levels at the CommHERE partner institutions, we now open up and invite all EU health research projects to participate in our communication network.”

The CommHERE project is one of the first communication projects to receive funding from the EU within the 7th Framework Programme on Health. It aims to improve communication on the outcome of EU-funded health research projects, mainly towards the media and the general public, in all of Europe and beyond.

site horizonhealth

What are the chances of female fertility after an ectopic pregnancy?

Posted on by Priscille Rivière

About 2% of pregnancies are ectopic, representing 15,000 women annually in France. They represent the development of the egg outside the uterus which can endanger the woman’s life in the absence of medical intervention. In developed countries, mortality linked to an ectopic pregnancy remains the exception; doctors are therefore interested in preserving subsequent fertility and thus the possibility for the women in question to become pregnant again. For the first time, researchers in the Inserm “Epidemiology of reproduction and infant development” team (Unit 1018 at the “Centre for Research in Epidemiology and Population Health”) compared all of the existing treatments for ectopic pregnancy with respect to their impact on natural fertility during the subsequent two years.

The conclusions of the study reproduced in the journal Human Reproduction indicate that the ability to have a normal pregnancy after an ectopic pregnancy (subsequent fertility) is not linked to the type of treatment, especially the conservation of the Fallopian tube in which the pregnancy was implanted

Woman holding a positive pregnancy test against white background©Fotolia

In 95% of cases, an ectopic pregnancy is implanted in a Fallopian tube. This is a medical emergency. The treatment consists in interrupting the growth of the egg and removing it. Three types of treatment may be used:

– Medical treatment by injection (intramuscular or directly into the tube) of methotrexate which destroys the egg and eliminates the ectopic pregnancy without damaging the tube.

– A so-called “conservational” surgical treatment in which the tube is incised to remove the egg, preserving the tube.

– A so called “radical” surgical treatment in which the tube is removed with the egg.

Each of these treatments successfully eliminates the ectopic pregnancy, and, thanks to the improvements in diagnosis, the woman’s life is hardly ever in danger in developed countries. The objective of doctors is thus the preservation of the woman’s subsequent fertility.

Depending on the gravity and urgency of the case, two types of situations could occur:

– on the one hand, so-called inactive ectopic pregnancies for which medical or surgical treatment may be decided

– on the other hand, so-called active ectopic pregnancies for which surgical treatment is necessary which may be conservational or radical.

For the first time in a single therapeutic trial, the Inserm researchers compared the fertility of women two years after the various treatments.

For this purpose, the researchers included women presenting with an ectopic pregnancy that was treated in the 17 French centres that took part in the study between 2005 and 2009. Just over 400 women were divided into two groups depending on the activeness (and seriousness) of the ectopic pregnancy. In each group, one of two possible treatments were selected through drawing lots  and the women were then monitored for two years.

In the first group, the cumulative fertility curves that reflect the number of pregnancies in patients during the two years of follow-up showed no significant difference between medical and preservation surgery. The intra-uterine pregnancy rate two years after the intervention was 67% following medical treatment with methotrexate and 71% after conservation surgery among the female research population.

In the second group, two years after treatment, 70% of the women who wanted to become pregnant again were able to achieve an intra-uterine pregnancy after conservation surgery and 64% after radical surgical treatment.

For the researchers, the results of this trial are an invitation to gynæcologists to reconsider the treatment they offer for ectopic pregnancies, taking account of the various factors governing subsequent fertility, the length of follow-up after treatment and patient preference as well as the risks inherent in each of the treatments.

As far as Perrine Capmas is concerned, “medical treatment should be prioritised in the case of an inactive ectopic pregnancy due on the one hand to patient preference but also to the lesser risk especially thanks to the absence of anæsthesia and surgery. In view, however of the absence of difference regarding subsequent fertility, surgical treatment should be offered initially to women who, it is feared, might not to stick to the treatment (supervision after medical treatment can be extended for several weeks)”.

 “In the case of ectopic pregnancies that require surgical treatment, doctors can reassure women that even radical surgery will not alter their chances of subsequently having a natural pregnancy”.

A chip that is 100% biocompatible to measure brain activity

Posted on by Priscille Rivière

Interpreting the signals emitted by the brain and translating them into commands usable by humans is a goal that researchers have been pursuing in the development of what is known as brain-machine interfaces. With respect to health, these interfaces could be used by people suffering from paralysis. Up to now, researchers have encountered technological difficulties because the sensors used to record brain activity do not yet do so with enough accuracy.

With the support of the Bioelectronics Department of the St Etienne Ecole des Mines, a research team headed by Christophe Bernard of INSERM Unit 1106 “Institut de neurosciences des systèmes” have designed a system for sensing brain activity that is 100% biocompatible and made of organic matter. The medium, which is only a few microns thick, is as thin and flexible as cellophane, and yet very tough. The model was tested on an animal suffering from epilepsy. The quality of the brain signal recorded was 10 times better than the traditional brain activity recording systems. The research was published in the Nature Communications journal.

Des nouvelles techniques au service de la santé, OpenVibe. Une interface cerveau-ordinateur ou ICO (en anglais Brain-Computer Interface ou BCI) permet à son utilisateur d'envoyer des commandes à un ordinateur ou à une machine uniquement par la pensée. © P Hirsch/Inserm

Man-machine interfaces have been playing a central role for several years in the diagnosis and treatment of certain conditions, in the movements of artificial limbs (exoskeletons) and even in the design of artificial sensory organs. In the case of brain-machine interfaces, the problem consists in detecting the signals emitted by the brain and translating them into commands that are usable by humans. These signals are used for diagnostic purposes (such as, for example, to determine whether a person is epileptic and which regions of the brain are responsible for the attacks), to link an artificial eye to the regions of the brain that process visual information or to control the movement of exoskeletons in people who are paralysed by recording the neurons in the regions of the brain that control the motor function of limbs.

For the capture of the maximum number of signals emitted by the brain, there is a need for direct contact with the central nervous system. This is very hard to achieve when using non-invasive measurement systems (i.e. electrodes placed on the head). Another disadvantage is that most of sensors used today are not biocompatible, thus triggering a defence reaction in the tissues, resulting in loss of signal after a certain amount of time. Finally, and this is the most important aspect, the signals detected are pre-amplified at a distance from the source, and this results in the presence of considerable interference on the recordings, thus preventing them being used to their best advantage.

One solution: organic transistors

The Bioelectronics Department of the St Etienne Ecole des Mines in Gardanne, the Institut de Neuroscience des Systèmes (INSERM Unit 1106) and the Microvitae SME at Gardanne have contributed a technological solution to these problems.

The researchers designed a system of brain activity sensors made of an organic material (based on carbon composites) that is 100% biocompatible. The medium is only a few microns thick, as thin and flexible as cellophane, and very tough.

But the revolutionary technology lies in enabling the recording site to work as an organic transistor that amplifies the signal locally. The system was tested in an animal model suffering from epilepsy. The quality of the signal was amplified tenfold in comparison with the traditional systems an amount that the researchers claim to be considerable.

A technological solution such as this makes it possible to record numerous neurons and interface with brain structures in the long term. The immediate clinical applications could include assistance with diagnosing epilepsy and functional mapping in the context of neurosurgery for brain tumours. Naturally, these transistors could also be used for non-invasive recordings in direct contact with the head.

In addition to disease control, the technology will enable major advances to be made in basic research, and especially in the context of the Human Brain Project which has received one billion euros of finance from the European Union. Recording systems based on organic transistors are precursors to the Man-machine interfaces of tomorrow.

March 11th 2013

Posted on by Priscille Rivière

Sorry, this article is only available in French.

Launch of Constances, the largest epidemiological cohort study of the French population

Posted on by Priscille Rivière

Constances is a “generalist’ epidemiological cohort constituted from a representative sample of 200,000 adults aged 18 to 69. It has been organised by the Centre de recherche en épidémiologie et santé des populations (CESP – INSERM/Université Paris Sud/Université de Versailles Saint-Quentin-en-Yvelines) in partnership with the CNAMTS* and the CNAV and its purpose is to create a national database open to the public health research community.

Constances

Under the scientific and technical leadership of Marie Zins (CESP), Constances (CONSulTANts des Centres d’Examens de Santé), has already recruited 14,000 subjects since it was initiated during the course of 2012. The patients were chosen by drawing lots from the CNAV** database and received a letter asking whether they would participate in the cohort. Upon entry into the cohort, the volunteers benefited from a complete health check at the Social Security Health Examination Centres and this check will be repeated every five years. With the help of a questionnaire to be completed annually, they will be providing health information, their lifestyles (work, food, alcohol or tobacco consumption, etc.), and their environment social. This data will be compared with that of the Caisse nationale d’assurance vieillesse** and in the health insurance fund to find out when they were off work sick, the costs of care submitted for reimbursement and the hospitalisation data as well as their social life and careers. Blood and urine samples will also be preserved for the purpose of creating a “biobank”.

The “Investments in the future” programme has been labelled a national biology and health infrastructure. This research project and the creation of this very significant sample (the largest in France and one of the largest in Europe) monitored over time (cohort) has been designed as an “open epidemiological laboratory” accessible to the French and international research community, also acts as a tool that provides those in charge of public health with diversified sources of information about the population’s health, including risk factors, how the health care and the prevention system are used and the medical, occupational and social history of the subjects involved.

“Constances is a generalist cohort but we have stressed the process of ageing and chronic conditions, occupational hazards, women’s health, socially determining factors and social inequalities”

explains Marie Zins.

* Caisse nationale de l’assurance maladie des travailleurs salariés [National Health Insurance Fund for Employees]
** Caisse nationale de l’assurance vieillisse = Old Age Insurance Fund

Seven genetic risk factors associated with AMD

Posted on by Priscille Rivière

An international group of researchers has discovered seven new regions in the human genome associated with an increased risk of developing age-related macular degeneration (AMD), one of the main causes of blindness. Thierry Léveillard, INSERM’s director of research at the Institut de la Vision (INSERM / UPMC / CNRS), is coordinator of the European AMD Gene Consortium group, an international network of researchers representing 18 research groups. The results were placed online on 03 March 2013 in the journal Nature Genetics.

 

DMLA atrophique

© Inserm

AMD affects the macula, the region of the retina responsible for central vision. It is thanks to the macula that a human being can perform certain tasks requiring good visual acuity, such as reading, driving and recognising facial features. As AMD progresses, the performance of such tasks becomes harder and is eventually impossible. Although certain forms of AMD are treatable if the condition is detected sufficiently early, there is no cure.

Scientists have shown that age, diet and smoking affect the risk of a person developing AMD. Genetics also plays an important role. AMD is often hereditary and is most common in certain population groups.

In 2005, researchers showed that certain variations of the coding gene for factor H of the complement – a component of the innate immune system – are associated with a serious risk of developing AMD.

In this new study, the AMD Gene Consortium collected data from 18 research groups in order to increase the power of previous analyses. An analysis by the consortium consisted of data taken from more than 17,000 AMD sufferers, and these were compared with data from more than 60,000 individuals not suffering from AMD. The current analysis identified seven new genetic regions associated with the condition. As in the case of the 12 regions previously discovered, these seven regions are dispersed throughout the genome, indicating genes and functions that affect AMD.

“The challenge represented by the genetic complexity of AMD could be overcome by an association between all the centres working on this condition that causes blindness throughout the world; this is a demonstration of how union is strength”

, explains Thierry Léveillard, INSERM director of research at the Institut de la Vision (INSERM/UPMC/CNRS), co-ordinator of the EU-JHU sub-consortium, whose members consist of various European and U.S. centres that have played an important role in this study.

Since 2005, a total of 19 regions have been identified as being associated with AMD. They involve a variety of biological functions, including regulation of the innate immune system, maintaining cell structure, the growth and permeability of blood vessels, the metabolising of lipids and atherosclerosis.

As with other common conditions such as type II diabetes, the risk of an individual developing AMD is probably determined by not one but several genes. A more complete analysis of the DNA of areas surrounding the 19 regions identified by the AMD Gene Consortium could indicate several rare genetic variations that might have a decisive effect on the risk of AMD. The discovery of such genes could considerably improve scientists’ understanding of the pathogenesis of AMD and contribute significantly to the search for more effective treatments.

According to José-Alain Sahel, Director of the Institut de la Vision (INSERM / UPMC / CNRS): “

Without the methodical and coordinated clinical identification work performed at all the centres, the identification of such markers would be random. These clinical relationships will soon be very important in the application of predictive and personalised medicine.” 

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