Menu

Yes, the time change has physiological effects

The Black Sun©Fotolia

On the night of Saturday 29 October to Sunday 30 October 2016, at 3 am it will be 2 am. This time change is not without effects on human physiology and health. When, in April 1784, Benjamin Franklin wrote in the Journal de Paris that getting up an hour earlier in winter would reduce the consumption of candles and reduce pollution, he was right. When he claimed that the new schedule would be difficult to endure for only two or three days because “Only the first step costs,” he was wrong.

The scientific literature shows that the time change can lead to sleep and alertness problems, road accidents, depression, suicide, and myocardial infarction.

The transition is more disruptive in winter for those who go to bed early. For Claude Gronfier, Inserm Researcher, “Among other things, the time change causes problems with sleep and attention. Children and older people are particularly affected, and take around a week to adapt to the new schedules.”

To find out all about the change in time, its history, its impact on health and how that works, contact Claude Gronfier.

Creation of first accelerators of technological research at Inserm

batiment ART Ultrasons biomédicaux

Inserm is launching its first accelerator of technological research according to the objective that is part of the Institute’s strategic plan 2016-2020. This first “Biomedical Ultrasound” ART will be dedicated to research and the use of ultrasound in medicine, particularly in the field of cancer diagnosis and treatment, as well as cardiovascular and neurological diseases. This new therapeutic framework consolidates multiple skills within a single unit in order to develop a high capacity for innovation and to provide this to other Inserm laboratories or hospitals. The biomedical ultrasound ART will be based at ESPCI Paris, a talent pool for future leading engineers and researchers.

Research is now becoming more and more interdisciplinary in order to compete and to generate real progress. This is the philosophy behind the first accelerator of technological research established by Inserm in the field of biomedical ultrasound. To achieve this goal, physicists, biologists, clinicians and engineers capable of taking the technological constraints into account, are translating the concept into usable and transferable tools for other researchers and physicists that will be working at the same site.

 

Innovations stemming from the “Biomedical Ultrasound” ART will be designed so that they can be transferred to other Inserm laboratories or hospitals within the three major areas of medical research — cancer, cardiovascular diseases and neuroscience.

Researchers hope to offer in the near future:

– Instruments capable of treating heart failure without surgery;

– Miniature imaging systems for brain activity;

– Brain-computer interface for treating major neurological disorders such as depression;

– Portable smart sensors capable of measuring and storing a variety of functional parameters;

– Ultrasound imaging systems for the remote delivery of drugs to tumours under perfectly controlled conditions, or to activate these drugs remotely in the targeted area only.

A group of high-level Inserm engineers will continue to accompany the physicists from the “Wave Physics for Medicine” team (Inserm/CNRS/ESPCI Paris) led by Mickael Tanter, in order to further the development of new technology emerging from the laboratory. These engineers will also be in charge of making this technology simple to use, consistent with medical standards, training new users and constantly improving the performance of these tools.

 

“In order to make major medical advances, it is now becoming more essential to provide innovative technology shortly after its creation. Many interdisciplinary partnerships already exist between hospitals, research centres and our “Wave Physics for Medicine” team. Our laboratory has already been the source of major industrial success, such as SuperSonic Imagine (Aixplorer ®) and Echosens (Fibroscan®), two devices now used by medical teams to reduce liver biopsies for cases of hepatic fibrosis and for cases of suspected cancer tumours. Many other discoveries are currently being developed and our collaborations will be helped and strengthened by ART staff dedicated to deploying technologies to partners. The “Biomedical Ultrasound” ART shall act as a genuine accelerator for new discoveries in medicine” says Mickael Tanter.

The ART will be housed on the new premises at ESPCI Paris (City of Paris Advanced School of Industrial Physics and Chemistry) located in the heart of Paris.

 

About Inserm

Created in 1964, the French National Health and Medical Research Institute (Inserm) is a public scientific and technical research establishment, under the joint supervision of the French Ministry of Education, Higher Education and Research and the French Ministry of Social Affairs, Health and Women’s Rights. Inserm is the only French public body dedicated to biological and medical research and human health, and occupies a position along the entire pathway from the laboratory to the patient’s bedside. Its researchers study all diseases from the most common to the most rare.

With a budget of €998 million in 2015, Inserm supports nearly 300 laboratories distributed throughout France. Together the teams comprise nearly 15,000 researchers, engineers, technicians, managers, clinician-researchers, post-doctoral fellows, etc.

About ESPCI Paris

ESPCI Paris is unique place at the centre of Montagne Sainte-Geneviève in the fifth arrondissement, which combines education, research and innovation. The school is characterised by its high-level scientific training and interdisciplinary approach, strongly backed by research excellence, combining fundamental science and openness towards applications and innovation. Housing 9 joint research units (UMR), the school is recognised worldwide for research excellence in fundamental and applied science and drives innovation within the industry. It was founded as an engineering school in the City of Paris in 1882. A paragon of French education, the school has 6 Nobel Prize laureates since its inception. The “Wave Physics for Medicine” team from the “Waves and Imaging” unit at Institut Langevin is based at the school.

Saturday 29 October: World Stroke Day

A stroke, or cerebrovascular accident (CVA), occurs when the blood circulation to the brain is interrupted by the formation of a blood clot that blocks an artery in the brain, known as a cerebral infarction, or by the rupture of an artery in the brain, a situation known as a cerebral or meningeal haemorrhage.[1] As a result, nerve cells are deprived of the oxygen and nutrients they need and die, causing irreversible damage or sudden death.

In France, stroke is one of the main causes of mortality and the leading cause of physical disability acquired in adulthood.

Organised on the 29th of October every year, Annual Stroke Day is aimed at alerting the public on the need for immediate care as soon as the first symptoms appear: a numbness, weakness or paralysis in one or more limbs or in the face, loss of vision, difficulty in speaking, a problem with balance or a sudden headache.

 

The researchers in Unit 1171, “Degenerative and Vascular Cognitive Disorders” (University of Lille, Inserm, Lille University Hospital), work throughout the year to improve the current treatments and develop additional therapies. In a clinical study conducted in collaboration with teams from the Netherlands and the United Kingdom, Prof. Charlotte Cordonnier and her colleagues suggest a modification of the recommended treatment for patients who have suffered an intracerebral haemorrhage while regularly taking aspirin. The researchers found that platelet transfusion increases the long-term risk of death and disability compared with standard care without transfusion. Read the press release.

Prof. Cordonnier also studies hypothermia as a treatment for acute ischaemic stroke, as part of the European clinical trial EuroHYP-1, which she is coordinating in France. To find out more, visit the study website.

 

Meanwhile, research conducted by Jean-Claude Baron, a researcher at Inserm Unit 894, “Psychiatry and Neurosciences Research Centre,” has shown in an animal model that an oxygen mask almost completely prevents neuronal loss, and completely prevents sensorimotor deficits following acute stroke. A European study is underway to study this treatment in humans, which consists of a simple oxygen bottle and a light face mask.

Read the press release.

Researchers Régis Bordet, Charlotte Cordonnier and Jean-Claude Baron are available to answer your questions.

[1] To find out more, see the Inserm information file on the theme

The French are overweight – confirmed by the Constances cohort

100000 constances

Nearly one in two French people over 30 years of age are overweight. This is what the first results from the Constances cohort has revealed. Now supported by Inserm and the French national social security organisation for salaries workers (Cnamts), Constances collates health data on more than 110,000 French people. With ultimately 200,000 people monitored, Constances will provide varied indicators of health in the population, such as the influence of various factors on the occurrence of disease or the impact of preventive measures.

These results are published in the Bulletin Epidémiologique Hebdomadaire (BEH ) from Santé Publique France.

 

The Constances cohort is a unique research project in France, launched in 2012 following a pilot phase in 2009. Constances now collates health data from more than 110,000 volunteers aged 18 to 69. The volunteers, members of the French general social security system, were selected at random. Every 5 years, they are invited to undergo a health examination in one of 22 health examination centres run by the social security system spread over 20 regions, completing a questionnaire every year. Involving the health examination centres in implementing the Constances cohort is consistent with their historical role among people falling outside the French healthcare system.

“Data from the cohort are used to analyse the state of health of the French population and to give a better understanding of what happen throughout life. After several years spent recruiting, we have been able to analyse the data and provide the first estimates, particularly about the prevalence of excess weight and obesity” explains Marie Zins, Inserm coordinator of the Constances cohort.

Regarding the prevalence of excess weight and obesity, data have been studied from nearly 29,000 participants aged 30 to 69 years old in 2013. Nearly one in two French people could be overweight and general obesity, defined as a BMI > 30 kg/m2, could be close to 16%, although abdominal obesity, defined as a waist measuring ≥ 94 cm for men and ≥ 80 cm for women, proves to be much more common (between 41.6% and 48.5%).

Graphique EN

These data confirm the trends observed in the ObÉpi survey (2012) that collects data every three years on the prevalence of excess weight and obesity. In this survey, participants are asked by telephone about their waist measurement and their weight. In Constances, unlike the ObÉpi survey, the protocol for measuring BMI and waist is standardised in the health examination centres, where healthcare professionals take the measurements.

Details about age and income are also included in study and data to identify places/regions, among the areas analysed, where obesity is most prevalent. These are the Nord, where the prevalence of obesity reaches 25.6%, and Meurthe and Moselle (22.9%). Paris is least affected by obesity, with prevalence of 10.7%.

Carte Obésité-Nom villes

Prevalence of general obesity in France © BEH no.35-36, 2016, Santé Publique France

Towards 200,000 volunteers

The French national adult cohort is funded by the ‘Investing in the Future’ Programme. Initially set up by Inserm, Cnamts and the University of Versailles-Saint-Quentin-en-Yvelines, the size and operation of the Constances cohort match other large cohorts being set up in Europe. European collaborations already enable very large scale research and unprecedented international comparisons.

The aim is to include 200,000 volunteers.

Are you a volunteer? Do you want to take part?

Details and conditions can be obtained by writing to rf.secnatsnoc@tcatnoc and on the website www.constances.fr

Science Machina: A CEA and Inserm exhibition

Explore the outer limits of the brain and matter, create unlimited energy, overcome pain, simulate the unattainable, etc. subjects dear to science fiction that are a now a reality for research laboratories!

The “Science Machina” travelling exhibition celebrates science and the fantastic machines at the heart of the most extraordinary discoveries and developments in recent years, which continue to broaden the scope for new possibilities. Speaking of machines, the exhibition will focus on the dialogue between man and machine and between genius and technology.

Discover these cutting-edge machines through photographs and comic-book art in a series of 12 diptychs.

 

When science meets the “ninth art”

The comic book is a key component of the exhibition as it depicts scientific machines in an unconventional way, thus bringing together the world of art and science.

The writer Felix Elvis has enlisted 12 comic book artists to take one of the research tools used or partly developed by scientists at Inserm or CEA, and to create a portrayal using comic-book art. Comics, fantasy, manga, etc. each illustration has its own world that reflects the diversity of machines, from the micropump to the supercomputer.

For further discussion, comment and post your questions on social networks using #sciencemachina.

Practical information

SCIENCE MACHINA,

An exhibition organised by Inserm and CEA.

29 October—03 November 2016

Utopiales de Nantes/International Science Fiction Festival

Cité des Congrès de Nantes, 5 rue de Valmy, 44000 Nantes

Audience: children aged 7 and over

 

Les Utopiales de Nantes

Since its inception in 2000, Les Utopiales, The Nantes International Science Fiction Festival, has been aimed at opening up the world of the future, new technologies and the imaginary to as many people as possible, and helping them to discover it in a highly qualitative way. Chaired by Roland Lehoucq, astrophysicist at CEA, the festival will take place from 29 October to 03 November 2016. As well as covering annual science fiction news, the theme this year will be “Machines”.

As part of this partnership, researchers at CEA and Inserm will participate in debates and discussions with science fiction authors on the issues surrounding these machines and their possible applications. The world of science does not have to be finite and, on the contrary, as a continuously evolving subject, science and science fiction have a close or even common language!

Machines for travel, exploration, service, modification, etc. a wealth of topics predicted by the fertile imaginations of science fiction authors that are researched by institutes today.

Global consortium receives €12 million to combat the Zika virus

PhotoCP Zika

(c) Fotolia

ZIKAlliance, a multidisciplinary and multinational research consortium coordinated by Inserm, has received €12 million from the European Union’s Horizon 2020 research and innovation programme to conduct a large-scale 3-year research project on Zika virus (ZIKV) infection in Latin America and the Caribbean.

 

The consortium, led by virologist Professor Xavier de Lamballerie (Inserm, IRD, Aix-Marseille University) includes the Oswaldo Cruz foundation (Fiocruz) the universities of Heidelberg, Leuven and Oxford, the Erasmus Medical Centre, the Leiden University Medical Centre, the Bonn University Medical Centre, the Fundação Bahiana de Infectologia foundation and Institut Pasteur among its 52 partners, located in 18 countries.

In France, 11 partners will work alongside Inserm on this project: the Instituts Pasteur in Paris and New Caledonia, Inserm Transfert, the Institute for Development Research [IRD], the Atomic Energy Commission [CEA], the National Centre for Scientific Research [CNRS], Aix-Marseille University, Institut Louis Malardé, Papeete, ANSES, University of Lyon and University of Rennes 2.

“Funding by the European Commission of this project, coordinated by Inserm, shows how much French expertise, through the multidisciplinary approach of the REACTing consortium[1], is recognised for its ability to organise and coordinate research in an emergency. ZIKAlliance is the outcome of the strong mobilisation of research leaders since 2015 to combat this emerging infectious disease,” says Yves Lévy, Chairman and CEO of Inserm and President of Aviesan, the National Alliance for Life Sciences and Health.

 

In a global effort to combat this international menace that has affected 73 countries and territories worldwide (WHO Zika Situation Report, 13 October 2016), the consortium, which is spread over 4 continents, will bring together many university disciplines to approach three main objectives.

Its first goal is to explore the repercussions of ZIKV during pregnancy, and the short- and long-term effects on newborns. Even though a link between Zika and microcephaly has been proven[2], the consequences of ZIKV for mothers and babies remain largely unknown.

ZIKAlliance will also explore the history of ZIKV in humans and their environment, based on the context of other arboviruses that affect the same populations, such as dengue and chikungunya. Consortium partners specialised in basic sciences will seek to characterise the virus and disease mechanisms, and identify drugs to control the viral infection. In the social sciences, the partners will analyse the cost and social repercussions of the disease, and will describe the beliefs and behaviours within the affected Brazilian population.

Another of the consortium’s objectives is to better organise research in anticipation of future threats of epidemics in the affected areas: it will establish a network of research centres in Latin America and the Caribbean prepared to study emerging diseases. This objective is being pursued in collaboration with two other consortia funded by the European Commission: ZikaPlan and ZikAction.

 

Vast medical cohorts will be studied in Latin America and the Caribbean. The main European research bodies will contribute to basic research programmes. Meanwhile, the partners in Africa, Asia and Polynesia, will take part in intercontinental epidemiological studies planned within the ZIKAlliance.

“We have managed to assemble a very large panel of partners whose experience is likely to make this project a success,” points out Xavier de Lamballerie, adding, “We are really trying to build something lasting that will help the regions in the event of future epidemics.”

A meeting to launch the project is planned in Sao Paulo on 4 and 5 December 2016.

ZIKAlliance is a 3-year project funded by the European Union’s Horizon 2020 programme for research and innovation according to Funding Agreement No. 734548.

[1] REACTing stands for REsearch and ACTion targeting emerging infectious diseases. Established in 2013, the REACTing scheme has made it possible to mobilise French teams for the chikungunya epidemic and for Ebola.

[2] See for example, de Araujo et al, Lancet Infect Dis, published online on 15 September 2016, DOI: http://dx.doi.org/10.1016/S1473-3099(16)30318-8

Gastroenteritis is back in metropolitan France

Sentinelles

Sentinelles network’s bulletin of 19 October 2016

According to the Sentinelles network’s weekly bulletin of 19 October 2016, the incidence rate of acute diarrhoea reached epidemic levels in metropolitan France last week, with 155 cases observed in general medicine clinics per 100 000 inhabitants.

The Sentinelles network adds that the current level of gastroenteritis is higher than the mean level observed in previous years in the same period. The Grand-Est, Ile-de-France and Pays de la Loire regions are particularly affected, with respective estimated incidence rates of 297, 213 and 211 cases per 100,000 inhabitants.

 

The Sentinelles network is national surveillance system developed by Inserm and Pierre and Marie Curie University. Made up of 1,300 general practitioners and about a hundred private paediatricians, it has allowed the development of large databases on several diseases, for health surveillance and research purposes.

To obtain further information on gastroenteritis in France, you may contact Thierry Blanchon, Deputy Head of the Sentinelles network.

Hepatitis C virus observed under a microscope for the first time

BO56374 éluats Fraisjc AR3A VLDL-0026b

(c) BMJ / British Society of Gastroenterology 2016

Scientists have finally observed the hepatitis C virus (or HCV) using an electron microscope. This is the first time since the virus became known in 1990. Inserm researchers at Tours (Inserm unit 966, “HIV and Hepatitis Viruses: Morphogenesis and Antigenicity”) have taken other scientists by surprise, including an American team believed to have accomplished this feat in 2013. The latter had in fact misunderstood the nature of the particles observed.

This research is published in the journal Gut.

 

The scientific community has waited twenty-five years for this. One of the greatest challenges of our era is to observe the hepatitis C virus, or HCV, under a microscope. It is responsible for 130 to 150 million cases of hepatitis C worldwide and about 700,000 deaths each year. This goal has become a reality thanks to the work by Inserm.

Viruses are normally discovered and described by observing them. However, HCV is an exception. All available data on this virus since 1990 were obtained by molecular biology as no one could view it under a microscope. This is due to the ability of the virus to hijack the machinery of the liver to give the appearance of a single lipid particle. This strategy allows the virus to easily penetrate cells and circumvent the immune system, also making it visually undetectable. “It resembles a single, small blank sphere amidst other blank lipospheres in the blood” explains Jean-Christophe Meunier, Inserm Research Fellow who is leading this study. “The virus takes advantage of the synthesis pathway for lipoproteins, particles that transport fat within an organism, so that it can replicate and closely associate with lipoprotein components.”

The virus effectively positions and attaches itself to the formation route of new lipoproteins and their components (phospholipids and their proteins).

Under its “disguise”, the virus becomes a genuine lipoviroparticle. This phenomenon was known for a long time, which makes it impossible to directly observe in the bloodstream of patients.

By contrast, lipoproteins sometimes inadvertently integrate viral proteins during formation, so it is possible to think that one is dealing with a virus when it is a single lipid particle. “This is precisely what happened in 2013 when an American team believed that they had observed the HCV virus”, explains Jean-Christophe Meunier.

 

Well-Structured Lipoviroparticles

Except this time, researchers are sure of their findings. They have used several viral protein-specific antibodies and were finally able to distinguish these famous lipoviroparticles from single lipoproteins circulating in the serum of individuals.

This work was possible through the electron microscopy platform at the University of Toulouse backed by the Inserm unit.

image VHC

(c) BMJ / British Society of Gastroenterology 2016

And as scientists observed, these chimeric particles ultimately have a similar structure to [lipoproteins]. They take the form of a sandwich lipid composed of a viral RNA centre, core antigen and enveloped by a monolayer of phospholipids. This is surrounded by a mixture of fatty acids and cholesterol, which are further enveloped by a second monolayer of phospholipids. Finally, the size of the virus varies according to the number of lipid layers it contains. “This structure is completely consistent with previous molecular biology work that predicted this formation. These observations validate twenty-five years of work for the scientific community.” says Jean-Christophe Meunier.

image VHC 2

(c) BMJ / British Society of Gastroenterology 2016

Apart from the satisfaction of accomplishing this technical feat, researchers stress the relevancy of this work. “Effective treatments are now available for hepatitis C, but a vaccine has yet to be found. Now, knowing the exact structure and organisation of these lipoviroparticles will be highly beneficial for those working in the field.”, states Jean-Christophe Meunier.

Combating Ebola: Encouraging Results for the PREVAIL Clinical Trial

DSC_0094

(c) Inserm/Anglaret, Xavier/Sissoko, Dadoua

An international research team involving Inserm and the National Institutes of Health (NIH) has just published the results of the PREVAIL study on treatment for the Ebola virus. While not definitive, the results show that ZMapp may benefit patients with the Ebola virus disease.

These results are published in The New England Journal of Medicine.

 

In this trial conducted in the context of the Ebola epidemic in West Africa, the effectiveness of the experimental drug ZMapp[1] was compared with the best supportive[2] care given at treatment sites. Used in combination with current care, ZMapp was well-tolerated and is leading to a higher survival rate than supportive care alone. However, the decreasing epidemic trend in West Africa at the time of the trial prevented the enrolment of a sufficient number of participants to prove this point definitively.

ZMapp is a combination of three antibodies that target a protein on the surface of the Ebola virus. By binding to the virus in an infected individual, they block its ability to infect human cells. It is believed that this blockade provided by the drug and administered as early as possible reduces the growth of the infectious agent and allows the patient’s immune system to mount an effective response in sufficient time.

The study opened in March 2015. All patients (except the first patient) were enrolled in West Africa where the epidemic is ongoing: 5 in Liberia, 12 in Guinea, and 54 in Sierra Leone. Patients of all ages with Ebola infections were eligible. The average age of the participants was 24 years, and slightly more than half were women. Although the team planned to enrol up to 200 patients, the study closed in late January 2016 once it became clear that the epidemic was curtailed in this region.

This was a randomised, controlled trial. Each patient was assigned by lot into two study groups with different treatment strategies. One group only received the supportive care available at their treatment sites. In Guinea, this supportive care also included Favipiravir[3], an antiviral drug whose potential benefit against the Ebola disease was previously demonstrated by Inserm[4]. Meanwhile, the second group received supportive care plus three consecutive infusions of ZMapp over the course of one week including, where applicable, Favipiravir.

A total of 21 patients, nearly one-third, died during the study. To assess whether ZMapp was effective, the team compared the number of deaths in each group after 28 days.

8 patients out of 36 (22%) died in the group that received ZMapp, compared to 13 patients out of 35 (37%) in the other group. This translates as a 40% lower risk of death among those who received the drug.

Given the lack of scope due to enrolment difficulties and insufficient staffing, this difference did not reach the statistical significance required to offer a firm conclusion. However, based on these results, the administration of ZMapp is approved should new Ebola cases arise in these 3 countries. This authorisation is issued under an expanded access protocol[5] (EAP, expanded access protocol).

According to Denis Malvy, Inserm researcher and co-investigator in this trial in Guinea: “The results from this trial mark a prominent step in treating the Ebola virus disease. I am also pleased that these results were obtained thanks to the unique partnership between researchers, authorities in Guinea and ONGs. I have no doubt that these collaborations will continue to bear fruit in the months to come.”

Inserm’s involvement in this clinical trial was made possible through the REACTing network (REsearch and ACTion targeting emerging infectious diseases) designed to:
• improve research planning during periods between crises: governance, preparation of research tools, identification of research priorities, application for funding, and ethical and legal aspects;

• fund and establish research projects during periods of epidemic crisis: coordination, strategic priorities, methodological assistance, and informing the authorities and general public.

This network is organised around a steering committee of some fifteen human health specialists, and relies on an 8-member scientific committee and methodological centres located in the North (F. Mentré, Bichat University Hospital) and in the South (A. Fontanet, Institut Pasteur). REACTing does not target any particular disease, and can get involved in all emerging infectious diseases. Its scope of action is broad, from fundamental research to human and social sciences, promoting a cross-disciplinary approach.

Guinea’s involvement (also called JIKIMapp) in the PREVAIL trial was led by the JIKI team at the treatment site in Forécariah, Coastal Guinea, directed by the French Red Cross. This study is part of the ongoing pioneering trial to assess the antiviral drug Favipiravir in Guinée-Forestière between December 2014 and April 2015.

Financial or logistic support for the trial was provided by NIAID/NIH; the French Institute national de la santé et de la recherché médicale (INSERM); the Republic of Sierra Leone Armed Forces; the Ministries of Health and U.S. Embassy staff in Liberia, Sierra Leone, and Guinea; the U.S. Centers for Disease Control and Prevention (CDC) and the CDC Foundation; the U.S. Biomedical Advanced Research and Development Authority; and the U.S. Defense Threat Agency. The trial was conducted in partnership with other academic, governmental and non-governmental agencies, including Bordeaux University Hospital, in the Franco-Guinean area.

[1] Made by Mapp BioPharmaceutical Inc. of San Diego, CA, USA

[2] Among other things, this optimised supportive care includes administering fluids, balancing electrolytes, maintaining physiological functions, reinstituting nutrition and treating other infections if they occur.

[3] Made by laboratories in Toyama/Fujifilm, Japan

[4] http://presse.inserm.fr/resultats-definitif-de-lessai-jiki/22789/

[5] An EAP is a U.S. regulatory mechanism that enables an unlicensed drug to be made available to treat a serious or life-threatening disease for which no approved therapy is available. The U.S. Food and Drug Administration has approved the EAP for use in the United States.

Rituximab effective in the treatment of membranous glomerulonephritis

A national trial on membranous glomerulonephritis in 80 patients was coordinated by Prof. Pierre Ronco, of the Department of Nephrology and Dialysis at Tenon Hospital AP-HP, of the Inserm Unit “Rare and common kidney diseases, matrix remodelling and tissue repair” [1] and Pierre and Marie Curie University, and by Dr Karine Dahan, of the Nephrology Day Hospital at Tenon Hospital AP-HP. This serious autoimmune disease is the most common cause of nephrotic syndrome in adults. In 30% of cases, it progresses to very severe renal failure. Conducted in collaboration with Prof. Tabassome Simon, from the Department of Clinical Pharmacology and East Paris Clinical Research Centre at Saint Antoine Hospital, AP-HP, this trial shows, for the first time, the efficacy and safety of rituximab in treating the disease.

This work was published on 27 June 2016 in the Journal of the American Society of Nephrology.

 

Membranous glomerulonephritis is a rare autoimmune disease (one new case recorded per year per 100,000 inhabitants), in most cases caused by antibodies directed against a protein (PLA2R) located in the renal filter (the glomerulus). The immunosuppressive treatments – aimed at attenuating this immune reaction of the body – that have been used until now have shown some efficacy, associated, however, with considerable toxicity: risks of infection, fertility problems, subsequent development of cancer or impaired renal function.

Rituximab is a monoclonal antibody specifically directed against the B lymphocytes that produce the toxic antibodies. Until now, its safety and efficacy had not been demonstrated.

In this context, Prof. Pierre Ronco and Dr Karine Dahan conducted a study in 80 patients with a severe form of membranous glomerulonephritis at Tenon Hospital AP-HP. The patients were enrolled from January 2012 to July 2014 in 31 nephrology departments throughout France, including 9 departments of Paris public hospitals (AP-HP) [2], with annual follow-up for two years.

This randomised study made it possible to compare the efficacy of the standard treatment, known as “antiproteinuric,” with the same treatment combined with 2 intravenous infusions of rituximab (375 mg/m2) given at a one-week interval. Patients were observed for the occurrence of immunological remission (disappearance of antibodies), clinical remission (reduction or disappearance of proteinuria) and adverse effects of the treatment.

Results showed that rituximab had a positive effect on immunological remission (50% from 3 months) and clinical remission (with 64% of patients entering remission before the end of the study), with corresponding values of only 12% and 34% respectively in patients given the antiproteinuric treatment alone.

The percentage of remission was similar to that obtained with other immunosuppressive treatments, but with a much lower therapeutic risk, since the number of adverse events was the same in both treatment groups (with or without rituximab).

 

“This study contributes a very important element to the debate surrounding immunosuppressive treatments in membranous glomerulonephritis,” explains Prof. Pierre Ronco.

“In clinical terms, it favours the use of rituximab as a first-line treatment in severe forms, with very regular monitoring of the level of anti-PLA2R antibodies in these patients.”

This study will provide a basis for other protocols aimed at increasing the percentage of clinical and immunological remission without increasing the rate of adverse effects. It is likely that some patients did not respond to the treatment because the rituximab leaked into the urine. These protocols will therefore include the use of higher or more frequent doses, and further IV infusions in patients who maintain high antibody levels.

fermer