Osteoarthritis and metabolic disease: a “joint” therapeutic target?

© Fotolia

Osteoarthritis is an incapacitating condition with diverse etiologies, the most recently described of which is metabolic syndrome (MetS). For the first time, researchers from the “Molecular Engineering and Articular Physiopathology” (Cnrs/Université de Lorraine) and “Acute and chronic cardiovascular failure” (Inserm/Université de Lorraine) research laboratories in Nancy, France, have described the spontaneous development of this type of degenerative joint disease in a mouse model of MetS. Inserm researchers Hervé Kempf and Anne Pizard, together with their co-workers, have characterized the existence of osteoarthritic lesions of the tibiofemoral joint of the knee in the presence of metabolic disorders.

This new experimental model of metabolic-associated osteoarthritis has also made it possible to demonstrate that chronic treatment with a mineralocorticoid receptor antagonist (MCRA) improves joint impairment. This drug is already used in heart failure and has been proposed as possibly being more effective in obese patients.

This research has been the subject of a letter published in Annals of the Rheumatic Diseases.

For the researchers, “these results will make it possible to propose metabolic-associated osteoarthritis as a potential new indication for MCRA therapy”, a hypothesis that they intend to test in the clinical setting very soon.

Inserm Transfert has filed a patent application for this research.

MS : using MRI to predict relapse

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. It generally affects young people, in whom it is the leading cause of non-traumatic motor disability. This disability develops either progressively or in the form of relapses interspersed with periods of remission.

At present, magnetic resonance imaging (MRI) is widely used to diagnose and follow up patients with MS. However, no imaging tools exist to predict the onset of relapse.

MS is caused, at least partially, by inflammatory cells (notably lymphocytes) migrating into the brain and spinal cord through the walls of blood vessels. The cells migrate by binding to adhesion molecules that are present on the surface of these vessels.

Researchers from the “SpPrIng” team, led by Fabian Docagne at Inserm Unit 1237 in Caen, France, have developed an MRI technique in which the progression of the disease can be followed in space and time in a mouse model of MS. To do this, they used MRI-detectable iron beads that bind to the adhesion molecules.

In this study, published in the journal PNAS, the authors demonstrate that this technique is able to visualize the migration of the inflammatory cells, thereby making it possible to predict the onset of relapse in asymptomatic mice, and remission in sick mice.

This technique could in the future be adapted for use in humans to improve prognosis and follow-up in patients with MS.


In the right-hand image, the iron beads (in black) have entered the spinal cord, thus revealing inflammation

Malaria: new insights into the mechanisms of parasite entry into liver cells


3D model of a Plasmodium protein mediating parasite entry into liver cells. ©O. Silvie

Malaria remains a major cause of mortality in the world, especially in Africa. The disease is caused by Plasmodium parasites, which are transmitted by mosquitoes. In the first hours following infection, parasites injected by the mosquito migrate from the skin to the liver, where they initially multiply before infecting red blood cells.

Until now, the mechanisms of parasite entry into liver cells remained poorly understood. Using cell culture systems, the team of Olivier Silvie, researcher at Inserm (Centre d’Immunologie et des Maladies Infectieuses) showed that the main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, use distinct pathways to infect liver cells.

By employing a genetic approach in a rodent malaria model, the researchers identified a key parasite protein that determines which entry route is used. This work, performed by teams of Inserm and Universities of Paris, Strasbourg and Oxford-Mahidol, reveals new aspects of the host-parasite interactions.

The results open new perspectives for the development of antimalarial strategies aimed at blocking the early stages of infection.

Depression, cardiovascular risk… and the class struggle

Classes sociales

© Fotolia

Depression is not just one of the world’s most incapacitating illnesses – it also comes with an increased risk of cardiovascular disease, particularly that of the coronary arteries (angina and heart attack).

According to a study by Inserm conducted in 10,000 people followed up for more than 20 years, this risk is doubled in non-executive or blue-collar workers in relation to executives. These data come from GAZEL, a French cohort of former employees of what at the time was known as Électricité de France-Gaz de France (EDF-GDF), and have been analyzed by a multi-disciplinary team of psychiatrists, epidemiologists, and cardiologists. The depressive symptoms were measured in 1993 and then each cardiac event occurring during the follow-up period was carefully validated by a committee of experts.

This study shows that the lower the socioeconomic status of a depressed individual, the greater their associated cardiac risk. It also shows that this risk cannot be explained by health behaviors such as smoking or physical activity, thereby suggesting that depression could have a direct impact on cardiovascular health.

It remains to be understood why these mechanisms are more pronounced in non-executive or blue-collar workers than in executives. One plausible interpretation is an increased reactivity to stress when socioeconomic status is perceived to be low, as illustrated by certain neuroscientific studies. In any case, these results call for particularly close attention to be paid to the cardiovascular health of individuals with depression, and even more so in those with other psychosocial difficulties.

Measuring gray matter to predict recovery from coma

VisAGeS : Vision, Action et Gestion de l'Information en Santé


Predicting recovery from coma following cardiac arrest remains a question to which physicians do not have an exact response. When – and if – a critical care patient will recover consciousness is evaluated essentially by means of recurrent clinical examinations and the recording of brain activity. Researchers at Inserm (Inserm Unit 1214 Toulouse NeuroImaging Center) led by Stein Silva, have recently developed a method that uses magnetic resonance imaging (MRI) to predict such recovery. The results were published this month in Critical Care Medicine.

Coma is a state of prolonged unconsciousness during which the patient fails to respond to any stimuli, including pain. There are many possible causes of coma. It can, for example, be brought on by temporary loss of blood flow (ischemia) or oxygen (anoxia), both of which are essential for the brain to function. This scenario, which is seen with cardiac arrest, is one of the leading causes of coma both in France and worldwide. The disruption in blood flow brought on by the cardiac dysfunction leads to major and extensive aggression of the brain tissues: the gray matter, consisting mainly of nerve cell bodies (neurons), and the white matter, formed from the nerve fibers of these neurons. In this study, Stein Silva’s team explored the following idea: does cardiac arrest impact brain structure? If so, is the potential for neurological recovery from coma related to the degree and extent of this impact?

To study this hypothesis, the researchers used MRI to measure and then compare the volume of gray matter in comatose post-cardiac arrest patients and healthy subjects. Measurements were made of the gray matter in the cerebral cortex and in the sub-cortical structures located deeper in the brain, a few days after the cardiac arrest. The results show that precise quantification of the volume of gray matter in the brain revealed early and extensive brain atrophy in these patients. However, above all, these data indicate that the degree of this atrophy, measured several days after the onset of the cardiac arrest, is indeed associated with the potential for neurological recovery of patients, evaluated one year after the start of the coma. The greater the atrophy, the lower the chance of a favorable outcome for the patient. Finally, when going into greater detail, this research is in favor of the existence of key brain regions, whose anatomical integrity appears to be associated with the capacities to form conscious processes.

All in all, these results shed new light on the biological mechanisms necessary for the creation and maintenance of consciousness in humans. According to Stein Silva: “this research opens new avenues for evaluating the prognosis of these patients and means that we can consider innovative therapies focused on the protection and specific modulation of certain brain structures involved in the emergence of consciousness following cardiac arrest.”

A patient has been living with an artificial larynx for the 18 months

U1121 "Biomatériaux et Bioingénierie"

© Inserm/Delapierre, Patrick

In 2013, researchers from Inserm and physicians from the Strasbourg University Hospitals announced their success in developing an artificial larynx. Since the first time they began implanting this prosthesis five years ago in patients whose own larynx had been removed for health reasons, they have optimized both the implant and their surgical technique. Today, they are presenting the case of a patient who has had the implant for 18 months, a feat that has enabled him to regain his voice and sense of smell, breathe through his nose and mouth, and not have to use his tracheostomy tube.

In cases of severe laryngeal cancer, doctors can opt to perform total laryngectomy. However, in order to be able to breathe correctly, the patient will then need a tracheostomy, which is an opening created in the front of the neck. The impact on quality of life means that such a procedure is not without consequences for the patient, due in particular to the loss of voice and sense of smell. After a lengthy rehabilitation period, the patient can use the esophageal speech technique but the process is an arduous one.

Christian Debry, researcher at Inserm Unit 1121 “Biomaterials and Bio-engineering” and Head of the Department of Otolaryngology and Head and Neck Surgery at Strasbourg Hautepierre University Hospital, together with his co-workers has endeavored to develop an artificial larynx for these patients[1]. Since 2012, 6 patients have received such implants but their fragile state of health has meant that they have not been able to keep them. Last year, Inserm researchers had optimized the surface coatings of the implants by developing an antimicrobial film to prevent them from being rejected.

“This 56-year-old patient has been living with the optimized implant for more than 18 months. He has now regained his voice and sense of smell, which had been compromised by the surgery.  He is able to completely go without using his tracheostomy tube for long periods – both day and night. It is the first time that such a concept has proved itself. The patient does continue to have some difficulty swallowing but, nevertheless, an initial breakthrough has been made, which is an actual improvement in comfort and quality of life for these patients. Our ambition is to ultimately restore their ability to eat normally and that they rediscover the social aspect of mealtimes. The development prospects for this prosthesis remain considerable.” emphasized Christian Debry.

[1] with the company Protip Medical

Zika virus infects the human retina

Two Inserm teams involving Unit 1058, “Pathogenesis and Control of Chronic Infections” (Inserm/University of Montpellier/French Blood Transfusion Service) and Unit 1051, “Montpellier Institute of Neurosciences,” have just shown that Zika virus can infect the pigment epithelium of the human retina, and may thus be able to cause retinal damage.

This study is published in Journal of Virology.

Infection by Zika virus may result in several types of symptoms, particularly neurological damage of the Guillain-Barre type in adults and microcephalies in newborn children and infants. However, several studies suggest that the eye might be a preferred target of the virus, and ocular damage has been recently described in infected people.

Two Inserm teams have just demonstrated for the first time that the pigment epithelium of the human retina is permissive to infection by Zika virus. Using a human retinal pigment epithelium model derived from induced pluripotent stem cells, these teams were able to show that the virus replicates very efficiently in this type of cell. Moreover, the infection disrupts the integrity of the epithelium, and can thus have serious consequences for infected individuals, in terms of both visual function and viral transmission.

This study therefore emphasises the paramount importance of better characterising the ocular damage observed in certain individuals who have been infected by Zika virus

Smell, those neurons with a nose

Thanks to the receptors in our nose, we can identify thousands of smells. But there are still many grey areas regarding the mechanisms at work in sending information to the brain. Research conducted by Alexander Fleischmann and his colleagues at Unit 1050, “Center for Interdisciplinary Research in Biology” (Collège de France/CNRS/Inserm) provides a better understanding of the neural networks activated when an odour is perceived.

Issue 32 of Science&Santé magazine devotes an article to this discovery.


13/11 attacks: young people deeply marked

One year after the 13 November attacks, the survey “Conditions de vie et Aspirations” (Living Conditions and Aspirations) by CRÉDOC (Research Centre for the Study and Monitoring of Living Standards), part of the 13 Novembre programme initiated by Inserm, CNRS and héSam Université, reports on the strong impact of the attacks on the French population, particularly the young.

A sample of 2,000 people representative of the French population responded to a series of questions such as “Can you say which terrorist acts, committed in the world or in France, have affected you most since the year 2000? What are the main consequences of the attacks that occurred on 13 November 2015?”

From this survey, we particularly learn that:

80% of French people say they have been marked by the attacks of 13 November 2015, even though three quarters of them have no personal link to the victims or places involved.
65% of 18-24 year olds and 63% of 25-39 year olds show strong feelings of fear, compared with 54% of people above that age range
The existence of cultural and religious tensions within society is the reason most often invoked to explain the attacks, and for nearly 40% of the population, they are inexplicable acts.
26% of French people have a personal link to the events (victim, witness, familiarity with the places), and 25% consider that there is too much talk about the 13 November.

Note: the interviews took place before the attacks in Nice on 14 July, and before those in Saint-Étienne de Rouvray on 26 July 2016.

Exhibition « La Science a du gout »

Let’s discover how to eat well to live better!

A fun-filled, tasty and interactive exhibition about the joy of eating, balanced diet and health. Meet our scientists, learn while you play, and let your senses guide you through the workshops!

The Ministry of Higher Education and Research, INRA and Inserm invite you to this exhibition, which will send you on a journey to discover your senses. Accompanied by Hector, a taste receptor, you will learn about the mechanisms of taste with the help of lots of games and activities.

On this pathway from mouth to brain, you will discover the amazing biological processes at work while you are eating, as well as the latest scientific advances in the areas of nutrition and health.

Opening on 4 October at 4 pm at Gare de Lyon (Line M), Paris

The exhibition will tour 15 cities in France from 4 to 23 October 2016

See the programme on the Inserm website (in French)