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Month: September 2014

September 29th 2014: World Heart Day

Posted on by Priscille Rivière

World Heart Day, held on 29 September each year, is aimed at increasing the general public’s awareness of the risk factors for cardiovascular diseases (poor diet, lack of physical activity, smoking and harmful use of alcohol), and thus helping to prevent them.

These diseases, which are associated with malfunctioning of the heart or of the blood vessels that supply it, caused 17.3 million deaths in 2013, i.e. 30% of all deaths worldwide.1 The most common cardiovascular diseases include coronary disease, heart rhythm disorders (arrhythmias), and cerebrovascular diseases, which affect the blood vessels in the brain.

The theme for this year’s event is: “Heart-healthy environments”

1 Source : World Health Organization

Our last communications on this topic :

Take care of your teeth to protect your heart – November 2013
NanoAthero: using nanomedicine to treat cardiovascular diseases – February 2013
Job strain and coronary heart disease linked – September 2012

Inserm is celebrating its 50th anniversary: Key events for the remainder of this year

Posted on by Priscille Rivière

To mark its 50th anniversary, Inserm is meeting the public and organising many events all over France. An opportunity to better understand the current issues in research with the help of the Institute’s staff, partners and supervisory bodies.


Key events for the remainder of this year:

The next free Citizen Conferences, “Santé en Questions” (Questions in Health), organised by Inserm and Universcience, will take place at 7:00-8:30 pm on 25 September, 16 October and 27 November, at the Cité des Sciences et de l’Industrie, Paris, as a simultaneous event with regional players involved in scientific and technological culture. The respective themes are “Mental health: new approaches,” “Pollution and endocrine disruptors: what are the risks?” and “HIV: what are the medical advances in France?”
For further information on the conference programmes, please visit the Inserm blog “Santé en Questions” and the Cité des Sciences et de l’Industrie website.

Since July, the Science Tour, an educational road show, has been touring France to meet the general public and students. It features educational and fun elements (an interactive exhibition, experiments, games, models, investigations and films).
For further information on the programme, and to find out when it is coming to your area, visit the Science Tour website.

Following on the success of the first two “Les Chercheurs Accueillent les Malades” (Researchers Welcoming Patients) days, Inserm is once again opening up its laboratories to patients and their families in order to encourage dialogue, discussion and questions. On Friday 3 October, on the theme of Nutrition and Metabolism, more than 80 researchers from Inserm, together with 9 partner patient associations, will welcome people affected by diabetes, obesity, haemochromatosis, lipodystrophies, chronic intestinal diseases and breast cancer. On Friday 28 November, the subject will be neurological and degenerative diseases. Researchers from Inserm, in partnership with 10 patient associations, will open up 30 laboratories to talk about advances in research and challenges involved in their work.
Information and registration on the CAM website.

The ceremony to award the Inserm prizes for medical research will take place on Tuesday 2 December at Collège de France. To conclude this 50th anniversary year, 8 prizes will be presented to women and men involved daily in building the scientific excellence of the Institute.

See the complete press file devoted to Inserm’s first 50 years at the Inserm press office

The INSIGHT study: to better understand the factors that trigger Alzheimer’s disease

Posted on by Priscille Rivière

Over 35 million people worldwide suffer from dementia, including Alzheimer’s disease [1]. In France, in 2014, approximately 900,000 people are affected, and the prevalence of the disease will increase considerably: an estimated 1.3 million people will be affected in 2020 [2], and over 2 million in 2040 [3], with more than 225,000 new cases reported each year.

World Alzheimer’s Day, which will take place on Sunday, 21 September, is an opportunity to review the progress of research and to present INSIGHT, a new study launched by teams from Inserm and the city of Paris public hospital system (AP-HP) at the Institute of Memory and Alzheimer’s Disease (IM2A) and the Brain and Spinal Cord Institute (ICM), working together in the Research Institute for Translational Neuroscience (IHU-A-ICM), and in collaboration with Pfizer, in order to observe and understand the natural course of Alzheimer’s disease. INSIGHT is an ancillary study of the MEMENTO national cohort.

Etude de la maladie d'Alzheimer
A study of Alzheimer’s disease – Atrophy of the cerebral hemisphere due to Alzheimer’s disease

INSIGHT is an innovative study of Alzheimer’s disease, and one of the first in the world to monitor healthy subjects at-risk. This study holds great hope for understanding the disease, and its results may hold promise of future treatments for patients.

“Research on Alzheimer’s disease, and more generally on pathologies associated with memory disorders, is evolving rapidly. Today we can recognise the disease very early, through a biological signature that can be identified in all patients. What we now want to explore are the endogenous and exogenous conditions for progression of the disease: why and how it occurs in some subjects but not in others,” explains Professor Bruno Dubois, Director of IM2A (Institute of Memory and Alzheimer’s Disease, located at La Pitié Salpêtrière Hospital in Paris), Director of the Inserm Team “Cognition, Neuroimaging and Brain Diseases” at the ICM, and principal investigator of the study.

Research method
The project involves monitoring 400 healthy volunteer subjects aged 70-85 years, with normal memory function. Its objective is not to detect or treat disease, but to observe changes in these healthy subjects. Do they have brain lesions? Will they develop the disease? How long does it take for the initial symptoms to appear? For the duration of the study, these subjects benefit from the monitoring and support of one of the best teams in the world working on memory-related diseases. To date, nearly 220 subjects have already been recruited.
This single-centre study, which will be conducted entirely at the IM2A (Institute of Memory and Alzheimer’s Disease at La Pitié Salpêtrière Hospital, AP-HP) is itself an unprecedented challenge.

INSIGHT is an ambitious study made possible through an innovative new scheme in medical research, a multi-partner foundation that focuses the Investissements d’Avenir (Investment for the Future) programme via IHU-A-ICM and Pfizer, together with the teams at IM2A and ICM, on a shared objective, that of better understanding Alzheimer’s disease

[1] For information on this subject, see the 2013 report from Alzheimer’s Disease International
[2] Figures from the Inserm information pack on Alzheimer’s disease
[3] More information on the France Alzheimer and Related Diseases website

“Immortal” flatworms: a weapon against bacteria

Posted on by Priscille Rivière

A novel mode of defense against bacteria such as the causal agent of tuberculosis or Staphylococcus aureus has been identified in humans by studying a small, aquatic flatworm, the planarian. This discovery was made by scientists in the “Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes” (CNRS/IRD/Inserm/Aix-Marseille Université), working in collaboration with the “Centre Méditerranéen de Médecine Moléculaire” (Inserm/Université Nice Sophia Antipolis) and other national and international research groups (1). Their work, published in the journal Cell Host and Microbe on 10 September 2014, highlights the importance of studying alternative model organisms, and opens the way towards new treatments against bacterial infections.

ver plat

© Eric Ghigo Dugesia japonica infected by green fluorescent Legionella pneumophila bacteria (located in the intestines of the worm).

By studying an original model organism, an aquatic flatworm called the planarian, scientists have succeeded in identifying a novel mode of defense against bacteria such as the causal agent of tuberculosis (Mycobacterium tuberculosis). Present in a latent state in humans, this mechanism could be stimulated by pharmacological intervention.

Scientists in the “Infection, Genre et Grossesse” (I2G) team led by Eric Ghigo had the idea of working on the planarian Dugesia japonica after observing that the discoveries made using classic immunological models (such as the Drosophila melanogaster fruit fly or the Caenorhabditis elegans roundworm) were dwindling. Previously, this flatworm was mainly known for its extraordinary regeneration capacities (2), which make it potentially immortal (it cannot die of old age). It is also able to resist bacteria that are highly pathogenic or even fatal in humans, as discovered by the research team — the only one in the world to have initiated immunological studies on this organism.

To understand the reasons for such an efficient immune defense mechanism, the scientists studied the genes expressed by the planarian following its infection by bacteria that are pathogenic in humans,such as M. tuberculosis, S. aureus and the causal agent of Legionnaires’ disease (Legionella pneumophila). They were thus able to identify 18 genes that make the flatworm resistant against these pathogens.

The scientists focused on one of these genes – MORN2 – which is present in the human genome and was found to be essential for eliminating all the bacteria tested. The team over-expressed this gene in human macrophages, the white blood cells responsible for eliminating pathogenic agents by digesting them (a process called phagocytosis). Thus stimulated, the macrophages became capable of eliminating the S. aureus, L. pneumophila and M. tuberculosis bacteria as well as many other pathogenic agents.

Detailed study of the mechanism of action of MORN2 revealed that it favors the sequestration (3) of M. tuberculosis in an intracellular cavity (the phagolysosome) where the bacterium is destroyed. In fact, the causal agent of tuberculosis usually succeeds in escaping this fate, so the bacterium can then remain in a latent state in the cells and reappear when the immune system becomes weakened. This discovery thus opens the way towards new opportunities in the fight against M. tuberculosis, antibiotic-resistant strains of which are becoming increasingly widespread.

This research also demonstrates the usefulness of “exotic” model organisms such as the planarian. Indeed, the MORN2 gene has been lost during the evolution of classic model organisms such as the D. melanogaster fruit fly, although it has been conserved in humans. Without the use of this new model, the mechanisms of the human immune response discovered during this study would have remained unknown.

This work benefited notably from CNRS support via a PEPS (Projet Exploratoire Premier Soutien) funding scheme designed to support exploratory research projects based on the creativity of research teams.

(1) in France, the Centre Commun de Microscopie Appliquée (Université Nice Sophia Antipolis); in Italy, the department of Clinical and and Experimental Medicine in Pisa; in New Zealand, the Otago Genomics and Bioinformatics Facility.

(2) In 1814, JG Dalyell discovered that a planarian cut into 279 fragments could regenerate itself in 15 days to produce 279 new worms.

(3) via a mechanism called “LC3-associated phagocytosis”.

Benzodiazepines and Alzheimer’s disease: the risk increases with duration of exposure

Posted on by Priscille Rivière

Researchers at Inserm Unit 657, “Pharmacoepidemiology and evaluation of the impact of health products on the population,” report new results on the link between benzodiazepines and dementia. In this study, published in the British Medical Journal (BMJ), they confirm that the use of benzodiazepines for three months or longer was associated with an increased risk of developing Alzheimer’s disease after the age of 65 years.The case-control study shows that the longer the exposure, the closer the association. The researchers therefore recommend monitoring the proper use of these drugs and limiting their intake to the recommended periods.

Benzodiazepines are prescribed by physicians for symptoms of anxiety and sleep disturbances for a recommended period of several weeks. In 2012, a study by Inserm Unit 657, “Pharmacoepidemiology and evaluation of the impact of health products on the population,” had shown, for a French cohort, that subjects using benzodiazepines showed an approximately 50% greater risk of developing dementia compared with those who had never taken them. In this new study, the researchers set out to confirm the association in another cohort, particularly the potential dose-effect relationship.

The researchers studied the database of the Quebec Health Insurance Board (RAMQ) to analyse the development of Alzheimer’s disease in a sample of patients aged over 66 years and living in Quebec (Canada) who had been prescribed benzodiazepines. They identified 1,796 cases of Alzheimer’s disease and monitored them for a period of at least 6 years. To carry out the case-control study, they then compared each of these cases with 7,184 healthy people of corresponding age, sex and duration of monitoring.

Results show that the use of benzodiazepines for three months or longer was associated with an increased risk (up to 51%) of later developing Alzheimer’s disease.

“The association become closer with more prolonged exposure and with the use of long-acting benzodiazepines compared with short-acting benzodiazepines,” explains Sophie Billioti de Gage, a researcher at Inserm.

]In conclusion, the researchers stress that although the cause and effect relationship has not been proven, the stronger association seen with long-term exposure “supports the suspicion of a possible direct link, although benzodiazepines may also be an early marker of a state associated with an increased risk of dementia. “

Benzodiazepine use is frequent and more likely to be chronic among older people. Nonetheless, benzodiazepines are useful drugs for the treatment of transient anxiety and insomnia. The authors therefore call for greater awareness of and compliance with good practices in their use, such as appropriate prescription for a short period.

“This would help to ensure that use of these drugs is limited to several weeks, a period for which the researchers did not observe negative implications for the risk of subsequent dementia,” emphasises Sophie Billoti de Gage.

Alim Louis Benabid receives the 2014 Lasker Award

Posted on by Priscille Rivière

The 2014 Lasker Award has just been won by Alim Louis Benabid, Director of Inserm Unit 318 “Preclinical Neurosciences” from 1988 to 2006, and winner of the 2008 Inserm Prix d’Honneur for his work on deep brain stimulation for the treatment of Parkinson’s disease.

Since 1945, the Lasker Award has distinguished the most brilliant researchers who have contributed to major advances in the diagnosis, treatment and prevention of human disease. In the international community, it is widely considered a precursor to the Nobel Prize. Prof. Benabid is the 8th French person to receive this prize.

Prix d'Honneur Inserm 2008 : Alim-Louis Benabid

© Inserm/Latron, Patrice

Born on 2 May 1942 in la Tronche, near Grenoble, Alim Louis Benabid spent his childhood in Sétif in Algeria. He returned to France to attend secondary school in Grenoble, and received his higher education in medical and science faculties in Paris.
Following his hospital residency, Doctor of Medicine (1970), Doctor of Science in Physics (1978) and a period as Professor of Biophysics at Université Joseph-Fourier in Grenoble, he directed the Inserm Unit 318 “Preclinical Neurosciences” from 1988 to 2006.

Alim-Louis Benabid focused his research on several brain pathologies, especially tumours and abnormal movements, and developed the surgical technique known as stereotactic (or stereotaxic) surgery, which makes it possible to target certain areas of the brain with a high degree of accuracy. He extended its applications to the treatment of patients with drug-resistant Parkinson’s disease and the treatment of other brain disorders.

From 1987 to 1991, Alim-Louis Benabid and his team developed a technique that involves implanting electrodes directly into the brains of patients with Parkinson’s disease in order to apply high-frequency electrical stimulation. They were thus able to eliminate the motor symptoms (tremor, akinesia, rigidity) of the disease. This intervention shows remarkable efficacy, with very low morbidity, and allows a reduction in drug-based treatments. It presently constitutes the most effective surgical treatment for Parkinson’s disease, and also provides basic data of considerable theoretical value.

Alim-Louis Benabid has also extended the indications for deep electrical stimulation to other pathologies, namely dystonia, refractory epilepsy, and obsessive compulsive disorder.

The introduction of electrodes into the brain, a technology developed under his direction, was greeted as a major discovery by the international scientific community.

Alim-Louis Benabid has subsequently focused his efforts on understanding the mechanisms of action of high-frequency deep brain stimulation and demonstrating its potential long-term effects, including its neuroprotective effects, on the natural course of Parkinson’s disease. He is also eager to identify in detail the effective targets and neuronal networks involved in this intervention.

Yves Lévy, Chairman and CEO of Inserm, wishes to convey his warmest congratulations to Alim Louis Benabid: “This prestigious award is a fitting tribute to his brilliant work on Parkinson’s disease, which has significantly improved the everyday lives of patients. The awarding of this internationally recognised prize confirms the excellence of French biomedical research. It also emphasises the importance of carrying out basic research and high-level clinical research in parallel.”

A scientific advisor for the French Atomic Energy Commission (CEA) since 2007, today he combines his research in this area with research carried out in the field of nanotechnology for the CLINATEC project. Developed by the leaders of technological research at CEA, in partnership with Grenoble University Hospital, Inserm and the Université Joseph Fourier in Grenoble, this biomedical research laboratory, devoted to the health-related applications of micro-nanotechnologies, is responding to a major public health challenge: developing new therapeutic approaches for brain diseases.

Read and view the profile of Alim Louis Benabid, winner of the 2008 Inserm Prix d’Honneur :

Exposure of pregnant women to certain phenols may disrupt the growth of boys during foetal development and the first years of life

Posted on by Priscille Rivière

A research consortium bringing together teams from Inserm, the Nancy and Poitiers University Hospitals, and the Centers for Disease Control and Prevention (CDC, Atlanta, USA), and coordinated by the Inserm and University of Grenoble Environmental Epidemiology team (Unit 823), has just published an epidemiological study indicating that exposure to certain phenols during pregnancy, especially parabens and triclosan, may disrupt growth of boys during foetal growth and the first years of life. Bisphenol A was not associated with any definite modification in growth. These results are published in this month’s issue of the journal Epidemiology, September 2014.



bébé

©Fotolia



Pregnant women are exposed to several compounds that are widely produced and abundant in our environment. This is the case for parabens (used as preservatives in cosmetics and healthcare products), triclosan (an antibacterial agent and pesticide found in some toothpastes and soaps), benzophenone-3 (used in sun protection products as a UV filter), dichlorophenols (the precursors of which are used in the manufacture of indoor deodorisers), and bisphenol A (the uses of which include manufacture of polycarbonate-based plastics (plastic bottles, CD cases, etc.) and epoxy resins (lining of food cans, dental amalgams) . These compounds belong to the phenol family, and are endocrine disruptors.[1] Experimental studies carried out in vitro and on animals have indicated that these compounds interact with the hormone systems involved in growth and weight gain.

The study was based on 520 boys from the EDEN mother-child cohort established by Inserm, and supported specifically for the present project by ANSES (French Agency for Food, Environmental and Occupational Health Safety).

 Pregnant women participating in this cohort were recruited in the Nancy and Poitiers University Hospitals between 2003 and 2006, prior to the present regulations concerning bisphenol A. Growth of each child was assessed by ultrasonography during pregnancy, and by measuring weight and length/height from birth to the age of 3 years. A urine sample taken during pregnancy allowed measurement of biomarkers for exposure to phenols in the CDC Atlanta Environmental Health Laboratory for US biosurveillance programmes.

Results obtained by Rémy Slama, Claire Philippat and colleagues show that over 95% of the pregnant women were exposed to these substances, and that maternal exposure to some phenols may disrupt the growth of boys. More specifically, the researchers showed a negative correlation between triclosan levels and growth parameters measured at the ultrasound examination in the third trimester of pregnancy, and that parabens were associated with increased weight at birth and at three years.

It is known that accelerated growth in the first years of life may increase the risk of obesity in later childhood. The study did not identify any clear link between urinary concentrations of other phenols and ante- and postnatal growth of boys. Because the urinary concentration of bisphenol A varies widely, it was not quantified accurately in the present study, which relied on a single urine sample for each woman.

For the researchers, “this is the first study concerning these environmental contaminants based on growth data collected during pregnancy, at birth, and up to the age of three years. Previous studies were focused on just one of these periods, and were usually restricted to the study of bisphenol A, without including other phenols.

The research teams will now try to repeat these results for a new couple-child cohort (the SEPAGES cohort), for which numerous urine samples will be collected from each participant (mother and newborn) during pregnancy and the child’s first few years of life. This approach will make it possible to reduce errors in exposure measurement, and to identify the potential periods of greatest influence of phenols on the growth of children during childhood. Girls, whose sensitivity to phenols may differ from that of boys, will also be considered in this new couple-child cohort.


[1]The use of bisphenol A in packaging for foods for infants and young children was banned in 2013. This ban is due to be applied to all food packaging from 1 January 2015.

 

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