October 29th 2015: World Stroke Day

A Cerebrovascular Accident results from the interruption of blood flow to the brain. The deprivation of oxygen and essential nutrients causes brain cells to die, leading to permanent damage (speech or writing difficulty, memory problems, bodily paralysis to a greater or lesser extent), or even sudden death.

World Cerebrovascular Accident Day is organised on 29 October each year and helps raise public awareness regarding the importance of immediate care for victims from onset of initial symptoms (confusion, speech problems, trouble understanding, dizziness, etc.).

© Inserm, F. Koulikoff

Obesity: surgery corrects diabetes even before weight loss occurs

Each year, obesity kills 2.8 million people worldwide. When confronting morbid overweight—and its direct consequence, type 2 diabetes—surgery is used as a last resort. Strangely, in patients who have had such an operation, the diabetes disappears before and independently of weight loss. Inserm researchers, with the help of physicians from Bichat Hospital, AP-HP, have shown that the surgically reconfigured intestine might be at the root of this improved glycaemic control. This study is published in Gastroenterology.

Overweight, even to a mild degree, is never harmless. As a cause of cardiovascular disease, joint and muscle problems and the development of type 2 diabetes, it can lead to premature death.

When a person is so overweight that his/her health is under threat, there is sometimes only one solution, i.e. bariatric surgery to reduce the patient’s appetite. The most frequently offered procedures are sleeve gastrectomy and gastric bypass. Both of these solutions involve removal of most of the stomach. In sleeve gastrectomy, the stomach is reshaped so that it forms just a tube. In gastric bypass, the food pathway is modified: the surgeon directly connects a small pouch from the top of the stomach to the intestine, forming a “roux limb.” The rest of the stomach, through which food no longer passes, continues to supply the enzymes needed for digestion. These enter the food pathway further down the alimentary tract, at the Y intersection.

Curiously, although patients lose weight rapidly in the months following the operation, physicians have noticed a clear improvement in their type 2 diabetes, practically as soon as they leave hospital. How can this phenomenon be explained? For the researchers at Inserm, the answer is clear: surgery not only affects food intake, but also modifies intestinal metabolism.

In order to confirm their hypothesis, the scientists reproduced both techniques in an obese rat model.

Following bypass, the Roux limb became strikingly enlarged in the rodents, as the cells constituting it proliferated abnormally. Moreover, these cells expressed a type of glucose transporter on their surface that is unusual for the intestine. These observations were also found in patients following surgery at Bichat Hospital.

People with type 2 diabetes secrete insulin, but their organs no longer respond to it. The level of the sugar in the bloodstream is no longer controlled, and remains abnormally high after every meal, resulting in damage to the tissues.

“We labelled glucose in order to follow its metabolic fate. Following surgery, the patient’s newly reconfigured intestine, like that of the rat, begins to consume very large quantities of glucose,” explains Maude Le Gall, Inserm Research Fellow. It diverts dietary and blood glucose for its own consumption. This phenomenon, which develops after barely a few days, might contribute to the rapid improvement in glycaemia and the disappearance of diabetes.”

Gastrectomy, a different mechanism with a similar result

Although gastrectomy does not affect the size of the intestine, it also acts on its cellular function. Absorption of dietary glucose by the intestinal cells becomes reduced. Conversely, the number of cells secreting GLP-1 peptide, which is usually inadequately produced in obese people, increases considerably. GLP-1 acts on the pancreas to increase its production of insulin. As a result, control of glycaemia in response to nutrient intake is more rapid.

“These results prove that sleeve gastrectomy and gastric bypass, while they have very similar effects on diabetes, do not involve the same mechanisms,” adds Maude Le Gall. “At the same time, they indicate the major role played by the intestine in controlling glycaemia.”

Although more studies are needed to understand these processes, this discovery indicates that there is hope of finding new options for treating type 2 diabetes without recourse to surgery.


Radioactive sources discovered at the University of Bordeaux

Inserm is paying close attention to the level 2 incident, declared on 21 October 2015 by the French Nuclear Safety Authority (ASN), which occurred in a joint Inserm/University of Bordeaux laboratory.

Inserm notes that the University will implement measures requested by ASN for which it is responsible as the owner of the premises. Inserm will give the University its complete support.

For Inserm’s part, two staff members who were exposed have been examined by the preventive medicine service. Following medical tests, the individuals in question have been allowed return to work, and will be monitored regularly.

Fresh insight into the causes of infant and perinatal mortality in the Seine-Saint-Denis district

In 2012, the Île-de-France Regional Health Agency initiated a regional project aimed at Reducing Infant and Perinatal Mortality (RéMI). This initiative was primarily focused on Seine-Saint-Denis, a district characterised by excess infant mortality (death before one year of age) and perinatal mortality (foetal deaths and deaths in the first week of life). The 2 research reports ordered by the Agency under this initiative—including one prepared by Inserm, and officially submitted to its Director General yesterday—bring new clarity to the situation in the department.

The audit has made it possible to identify risk factors associated with the women’s personal situations: 50% of them were overweight or obese. 7% did not have access to Social Security at the start of pregnancy, and 9% were in receipt of State Medical Aid (AME), or were in a scheme for access to urgent care.

The expert reports on the deaths also underline that for three-quarters of them, deviations from good practice were observed in the care of the pregnant women.

33% of the deaths were judged potentially or probably avoidable, by acting on one or more of these deviations from good practice

Given this observation, ARS is launching 3 workshops bringing together professionals and those involved in perinatal care in Seine-Saint-Denis, which will run from November 2015 until March 2016, based on these areas of reflection.

A first step in personalising stroke management

The team led by Didier Leys and Régis Bordet (UMR-S 1171, Lille 2 University, Inserm, Lille University Hospital) has identified a biomarker that makes it possible to predict the risk of haemorrhagic complications from thrombolytic treatment following a Cerebrovascular Accident (CVA or stroke). This new marker could guide medical decision-making in difficult cases, particularly in severely affected patients, and thus help to prevent the risk of haemorrhage from thrombolysis.

© Inserm, F. Koulikoff

During a stroke, thrombolysis is used to break up the clot obstructing an artery in the brain. For the last 15 years, this technique has been considered a major advance in the management of this condition. However, this treatment must be used within 4.5 hours of the onset of the stroke, if the benefit of relieving the blockage is not to be undone by the occurrence of intracerebral haemorrhage. This benefit/risk balance thus limits its use, because, according to current estimates, only 15% of patients are eligible for treatment. However, the clinical reality suggests that other patients might also benefit from thrombolysis, even if administered at a later time, without the risk of haemorrhage. Nonetheless, one still needs to be able to predict the risk of haemorrhagic complication, for a given patient, with the help of a marker.

The team led by Professors Leys and Bordet, which includes medical neurologists and pharmacologists, proposed that inflammation following stroke, and particularly interactions between the cells of the immune system and the vascular wall, might be responsible. They demonstrated the role of polymorphonuclear neutrophils, a type of cell involved in immune reactions, in the haemorrhagic effect of thrombolysis in the brains of animals, prior to testing the hypothesis in a cohort of 846 patients, comprising patients from Lille and from Finland.

The clinical results, which are published this week in the journal Neurology, show that a high concentration of polymorphonuclear neutrophils is associated with an increased risk of bleeding in the brain following thrombolysis, and a poorer prognosis at three months. By refining these results, the team of researchers in Lille revealed that the ratio of these neutrophils to another type of white blood cell, the lymphocytes, is even more predictive: a ratio greater than 4.8 is associated with a 4-fold higher risk.

This discovery should enable the launch of a clinical study to test the extension of the therapeutic window in patients with a ratio indicative of a lower risk, leading to personalised management guided by a simple biological marker, which can be measured routinely when the patient is admitted.

Understanding the mechanisms involved also offers an approach to preventing the risk of haemorrhage from thrombolysis by modulating the inflammatory cascade with drugs that are already on the market.

Launch of the influenza vaccination campaign

Monday 12 October saw the start of the annual vaccination campaign, which will continue until the end of January 2016. Last winter recalled the potential seriousness of influenza, which severely affected the most vulnerable populations (mainly people over the age of 65).

To better control the influenza epidemic, Inserm has created the Sentinelles network, an information system based on a network of 1,300 general practitioners distributed throughout metropolitan France. These “sentinel physicians” report cases of influenza, diarrhoea or chicken pox on a weekly basis.

In this way, the Sentinelles network and Inserm monitor the progression of influenza throughout the year, and are in a position to anticipate peaks at national level. The health authorities thus receive the maximum amount of information, which allows them to adapt their resources for the better protection and care of citizens.sentinelles

Ovarian cancer: A promising approach for treating the most aggressive forms using targeted therapy

Thanks to work done at Institute Curie by a team led by Fatima Mechta-Grigoriou, Inserm Research Director, it is now possible to identify, among women with aggressive ovarian cancer, those who could benefit from a promising targeted therapy.inserm_5619

Métastase tumorale dans l’ovaire © Inserm/Evrard, Gilles.

The Stress and Cancer team (an Inserm/Institut Curie team designated by the French National Cancer League), directed by Fatima Mechta-Grigoriou (photo, right), has just taken a major step toward identifying women with an aggressive form of ovarian cancer who are likely to benefit from targeted therapy in the form of a MEK inhibitor.

Finding the Achilles heel of ovarian tumour cells

Moreover, BRAF activates the MEK signalling pathway[1] involved in the development of low-grade ovarian tumours. MEK inhibitors have therefore been proposed as a possible therapeutic solution for these cancers.“75% of ovarian cancers are high grade, i.e. highly aggressive. The mutation profile differs between low- and high-grade tumours,” explains Virginie Mieulet (photo, left), post-doctoral fellow and co-author of this work. “For example, alterations in the KRAS/BRAF oncogenes are present in 70% of less aggressive tumours, but in only 1% of aggressive tumours.”

Fatima Mechta-Grigoriou and her team show that prescription of MEK inhibitors could extend to high-grade tumours. Because the MEK pathway is activated in 50% of high-grade ovarian tumours, even in the absence of KRAS/BRAF mutations. Why? “Because of MAP3K8 accumulation,” explains the researcher. “This protein controls tumour progression by regulating the cell cycle and tumour invasion, thus playing a key role in the development of ovarian cancers.”

“The MAP3K8 protein might serve as a biomarker for identifying patients likely to benefit from a therapy based on MEK inhibition,” adds Fatima Mechta-Grigoriou, Inserm Research Director, “especially since it can be quite simply detected from a tissue section by our physician pathologist colleagues, who, incidentally, have helped us greatly in this work.”

While clinical trials are already underway to assess MEK inhibitors in low-grade ovarian cancers, everything seems to point to the interest of developing a clinical trial in women with high-grade ovarian cancer overexpressing MAP3K8, to evaluate the efficacy of this targeted therapy, in addition to the conventional chemotherapies.

[1] Because of the key role of the MEK signalling pathway in carcinogenesis—activation is observed in 30% of cancers—MEK inhibitors constitute a promising therapeutic approach. Clinical trials are currently underway for several tumour locations (skin melanoma, intestinal tumours, thyroid cancer, etc.).

Ovarian cancer affects nearly 4,600 women in France each year. An ovarian tumour can develop silently for quite a long time, and thus attain a large size before causing symptoms that induce the woman to seek medical advice. This explains why this cancer is often diagnosed at an advanced stage. It is responsible for 3,150 deaths per year. Treatment is based mainly on a combination of surgery and chemotherapy. The choice between the different treatment options depends on the morphology of the tumour cells, their rate of proliferation, disease spread, etc. Analysis of the molecular profile of tumours could soon contribute to this decision and improve management. In most women with ovarian tumours, combination chemotherapies (platinum-taxane chemotherapy) have been shown to be effective. However, once a recurrence is diagnosed, there is no really effective treatment at this time.

Inserm—a partner in World Arthritis Day: “Together Against Arthritis!”

On 12 October 2015, World Arthritis Day, a Research and Information Day, “Together against Arthritis” will be held at Espace Charenton, Paris, under the patronage of Mr François Hollande, President of France.Orthopde


Arthritis and musculoskeletal conditions affect 24% of the European population, and are the leading cause of disability after the age of 40. Research is therefore more than ever the major issue of the day. In many countries, this day will be an opportunity for researchers, patients and journalists to update their knowledge on the technological innovations and new scientific approaches that will enable better management of these conditions.

In Paris, in the 12th Arrondissement, Espace Charenton (from 8:30 am to 5:00 pm) will host researchers, who will present their latest work, and patients, for whom exchange and information sessions are planned. They will thus be able to learn directly from the source, from the researchers and rheumatologists present.

The highlight of the day, and open to all, will be the midday debate, “Comment réduire la mortalité et la morbidité des rhumatismes?” (How do we reduce illness and mortality from arthritis?), facilitated by Mathieu Vidard, a journalist with France Inter radio station.

Speakers for the day include:

Bruno Bonaz, Inserm Unit 836, “Grenoble Institute of Neuroscience (GIN),” will present a session on the potential use of vagus nerve stimulation, which has already proved effective in Crohn’s disease, in rheumatoid arthritis.

Claudia Montero-Menei, Inserm Unit 1066, “Bio-Inspired Micro- and Nanomedicines,” will present her research on microcarriers for repairing muscular and skeletal tissues.

Pascal Richette, Inserm Unit 1132, “Bone and Cartilage Biology: Regulation and Therapeutic Targeting,” will speak about gout and the metabolic diseases associated with it.

Finally, Karine Louati will answer the question, “Arthritis: why does it cause fatigue?”

To find out more, register for free and consult the programme, visit the website:

This national event is supported by Inserm, AVIESAN (National Alliance for Life Sciences and Health), the French Society for Rheumatology, the Courtin Arthritis Foundation (the first private foundation dedicated to supporting arthritis research in France), SOFMER (French Physical Medicine and Rehabilitation Society), CRI (Rheumatism and Inflammation Club), GRIO (Osteoporosis Research and Information Group), and many patient associations.

Inserm’s Associations, Research and Society mission contributed to organising this day

To develop dialogue and partnership between researchers and associations, Inserm has put in place a dual scheme which has operated since 2004: a think tank, the Patients’ Association Liaison Group (GRAM), and an operational structure, the Associations, Research and Society mission.

To follow new programmes, such as training seminars, thematic discussion meetings, laboratory open days etc. or schemes to facilitate interaction between researchers and associations, consult the website:

Rapid diagnosis of Ebola: the eZYSCREEN® test proves itself in the field

Announced at the end of 2014 during the final phase of research and development, the rapid diagnostic test for Ebola virus disease developed by the French Atomic Energy Commission (CEA), with support from the Inserm Jean Mérieux P4 high-level biological containment laboratory (Lyon), has been assessed in the field, including in Guinea, over a period of several months. This assessment now allows the test to be CE marked, leading to its authorisation for use as a diagnostic tool. The eZYSCREEN® test will thus help to enhance the available means of control, particularly by detecting residual sporadic cases among symptomatic patients, or by post-mortem identification.

The rapid diagnostic test for Ebola, developed in the public health emergency of 2014 and 2015 by a team from the Life Sciences Division (DSV) of CEA, with support from the Inserm Jean Mérieux P4 high-level biological containment laboratory (Lyon), allows diagnosis of the disease within 15 minutes, using a few drops of blood or serum. An agreement has been drawn up with the Vedalab company (Alençon), which manufactures it.

In contrast to laboratory tests, this easy to use field test does not require sophisticated instrumentation or even electricity, and can be used by non-specialist staff. The result is read directly and visually. Storage for eight and a half months at 30°C, and for 14 days at 45°C, did not affect its performance, proving its high robustness and stability.

The eZYSCREEN® test was assessed under real conditions, including in the Ebola Treatment Centres in Coyah and Forécariah in Guinea (French Red Cross), and part of the analyses were also conducted in Donka National Hospital (Conakry, Guinea). These studies ended in August 2015. 

The rapid test shows excellent specificity, eliminating almost any risk of false positive results, and an appropriate degree of sensitivity for its intended use, i.e. to very rapidly identify the maximum number of cases possible in situ with a view to preventing epidemics.

These results enabled CE marking of the eZYSCREEN® test for Ebola, which is essential for its use during the sporadic cases that continue to occur in Guinea and Sierra Leone. The objective is to be able to avoid the start of a new large-scale epidemic outbreak.

Discussions are underway between CEA and diagnostics industries in order to allow the widest possible distribution of the test.

For this body of work, the Technological Innovations for Detection and Diagnosis (Li2D/DSV) Laboratory in the CEA Marcoule Centre has just received the Societal Resilience Trophies Technological Innovation Prize for 2015, awarded by the French High Committee for Civil Defence.

CE Marking

“CE” marking was established within the framework of European legislation. It indicates that the product conforms to the community requirements incumbent on the manufacturer of the product. It must be affixed before a product is placed on the European market.

With respect to eZYSCREEN® tests for rapid diagnosis of Ebola virus disease, their conformity with European Directive 98/79/CE for in vitro diagnostic medical devices

Inserm International Prize 2008, Nobel Prize in Chemistry 2015

Inserm is pleased to have awarded its 2008 International Prize to Tomas Lindahl, who was today awarded the 2015 Nobel Prize in Chemistry.

On Wednesday, the Nobel Prize in Chemistry was awarded to Sweden’s Tomas Lindahl, American Paul Modrich, and Turkish-American Aziz Sancar, whose work on the role of cells in the repair of damaged DNA is finding applications in cancer treatments.

These three researchers, who studied the “cell’s toolbox,” received the award for their “study of DNA repair” following damage by ultraviolet radiation, for example, explained the Swedish jury.

In 2008, Inserm awarded a prize to Tomas Lindahl, former Director of Clare Hall Laboratories at Cancer Research UK. In this British establishment, Tomas and his team are constructing a map of the DNA repair mechanisms that enable the molecule to “defend itself” against carcinogenic elements. In particular, they have shown that the DNA molecule is more fragile than was thought. Tomas Lindahl demonstrated the action of DNA glycosylase, involved in the first phase of the repair process known as “base excision repair,” which removes the nitrogenous base from the damaged part of the DNA, thus releasing a sugar/phosphate structure which, when recognised by a specific enzyme, can then be repaired.

They also discovered another form of DNA repair, which employs AlkB enzymes and other DNA dioxygenases to remove alkylation damage.

Research by his group also focuses on the more medical issue of why some patients’ cells become resistant to chemo- or radiotherapy.In 2008, he stated, “It is always an honour to be recognised by one’s peers. When I received the letter from Inserm informing me of this news, I was delighted to be distinguished by my French colleagues.”

Yves Lévy, Chairman and CEO of Inserm, is pleased to see “an Inserm laureate being awarded the highest international scientific distinction. Today the mechanisms of DNA repair are one of the foundations of research in the life sciences and health.”

Inserm will present its Grand Prix 2015 and International Prize on 8 December next at a ceremony in Collège de France

One of the ADN repair mecanism explained by video