Multiple sclerosis : Mission Regeneration !


Why does multiple sclerosis progress more rapidly in some patients than others? Why do some patients with MS manage to regenerate their myelin, while others do not? Inserm researchers at Unit 1127, “Brain and Spine Institute” (Inserm/CNRS/UPMC) have demonstrated that lymphocytes play a major role in the remyelination process, and that they could possibly be exploited to develop new myelin regeneration strategies.

This work is published in Brain

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, causing progressive destruction of the myelin sheath that surrounds the axons and is essential for their protection and for the transmission of nerve impulses. The ability to repair myelin efficiently is a key factor in preventing progression of the disease. It is essential to understand why and how certain patients manage to better handle the disease than others.

In multiple sclerosis, T lymphocytes attack myelin as if it were a virus, which is abnormal, but it is also they that organise its repair, more or less well. Lymphocytes activate macrophages and microglia (other cells of the immune system), which in turn attract new stem cells to the site of the lesion in order to repair the damaged myelin. Previous studies showed that in some patients, the lesions are completely repaired while in other patients, once the lesion has appeared, it is never repaired.

To gain a better understanding of the phenomenon, the researchers at Inserm transplanted lymphocytes from healthy donors or patients with multiple sclerosis into demyelinated lesions in the spinal cord of mice.

Using this technique, the researchers showed that the problem was not associated with the first phase of recruiting cells capable of repair, but with the point where these cells differentiate in order to perform myelin repair. In patients with a strong capacity for remyelination, the lymphocytes send the appropriate signals to activate the microglia, which then enter a state of activation and bring about stem cell differentiation and myelin repair. In patients with a poor capacity for remyelination, the T lymphocytes do not allow activation of the microglia, affecting the entire repair cascade.

By comparing the secretion profiles of lymphocytes from patients with a strong or poor capacity for remyelination, the researchers demonstrated the existence of 3 molecules associated with good remyelination, and 3 associated with poor remyelination.

One of these molecules is CCL19, which is associated with poor remyelination capacity. The researchers propose a hypothesis whereby inhibiting this molecule would allow macrophages to attain a state of activation and could therefore affect the remyelination profile of patients. 

Since microglial cells and macrophages are essential elements in coordination and repair, these results could also contribute additional elements of information regarding other conditions such as amyotrophic lateral sclerosis (also known as motor neuron disease), Alzheimer’s disease and Parkinson’s disease.

“The study of lymphocytes from patients with strong capacities for remyelination is a promising route to the development of new myelin regeneration strategies. Moreover, the systematic study of their lymphocytes might make it possible to provide support for diagnosis and treatment and to develop precision medicine tailored to each patient,” explains Violette Zujovic, Inserm Researcher and main author of this work.

28 February 2017: International Rare Disease Day



The 28 February 2017 marks the 10th edition of World Rare Disease Day, with the slogan “Join us in making the voice of rare diseases heard.” While there are 7,000 known rare diseases, 80% of them genetic in origin, new rare diseases are regularly discovered.

According to the definition used in Europe, a disease is called “rare” if affects fewer than 1 person in 2,000.

Of the 25 million Europeans affected, over 3 million French people are directly concerned, or 4.5% of the population, although each condition affects fewer than 30,000 people in France.

Often chronic and progressive in nature, they affect patient quality of life, causing motor, sensory or intellectual impairment in 50% of cases, and a total loss of autonomy in 9% of cases.

Coordinated by Inserm, and a member of the Rare Disease Platform, Orphanet is the portal of reference on rare diseases and orphan drugs, offering open access to many services to enable patients to understand their disease and its consequences, and guide them through their care pathway by identifying diagnostic laboratories and centres of reference. By facilitating access to patient associations, it also helps them to overcome their isolation.

Inserm researchers remain committed to advancing research, on both improvement of patient care and the efficiency of existing therapies. Some examples of research carried out by Inserm on this theme are available at the Press Room :

Rituximab effective in the treatment of membranous glomerulonephritis, published on 7 October 2016.

Long term correction of hyperbilirubinemia in animal models of Crigler-Najjar syndrome after AAV vector-mediated liver gene transfer, published on 21 July 2016.

An effective drug for myoclonus-dystonia, a rare disease of the nervous system, published on 8 April 2016.

The origin of heart dysfunctions in myotonic dystrophy identified, published on 19 April 2016.

Epidemics: urgent need for action

Déplacement au colloque international consacré aux vaccins con© Présidence de la République – L.Blevennec

Over 200 delegates from world vaccinology gathered in Paris

Inserm and the Coalition for Epidemic Preparedness Innovations (CEPI) are holding a large conference entitled “Vaccines Against Emerging Infections – a Global Insurance” on 21 and 22 February 2017. It is especially aimed at emphasising the urgent need for action and the potential for developing vaccines in the area of world epidemic crises. François Hollande, President of France, attended this conference today, along with Yves Levy, Chairman and CEO of Inserm, underscoring the major commitment of French research in this area.

The occurrence of recent epidemics and pandemics has highlighted the relative inability of the world scientific and political community to effectively fight the spread of infectious diseases. The epidemic of Ebola virus disease in Western Africa and of Zika in the Americas are the most recent examples. However, there are other threats in the offing, e.g. from epidemics caused by coronaviruses (SARS, MERSCov), Chikungunuya and even Lassa.

In each of these situations, the existence of a vaccine could slow or even prevent the occurrence of an epidemic. In the case of the Ebola or Zika epidemics, an effective vaccine would have saved thousands of lives and prevented social and economic upheavals in the affected countries. For this reason, the Coalition for Epidemic Preparedness Innovations (CEPI) was launched during the World Economic Forum in Davos in January 2016 by its five founder partners: the Bill and Melinda Gates Foundation, the World Bank, the Wellcome Trust and the governments of India and Norway. At world level, many organisations are striving to combat epidemics. The objective of CEPI is to make it easier for them to join together in developing promising vaccine projects.

A year after this launch, CEPI and Inserm have convened 200 delegates from the vaccinology field to share their ideas at a large conference in Paris. In attendance: people involved in basic and clinical biomedical research from around the world, and delegates from WHO, non-government organisations, private industry, philanthropic bodies, etc.

For Yves Levy, Chairman and CEO of Inserm: “The Ebola epidemic proved that we can develop vaccines quickly in extremely difficult conditions. It also proved that one of the keys to success is the willingness of all those involved to work hand in hand. We now have to act quickly if we want to be ready to deal effectively with the next epidemics. This conference, which we have managed to arrange in Paris in record time, is aimed at creating novel partnerships between the different actors in vaccine research worldwide. It also reaffirms the major commitment and leading role of Inserm in this area.”

French institutions back the March for Science


On April 22, Earth Day 2017, the citizens of the world are invited to participate in a massive “March for Science.” The initiative was launched by US scientists in response to “new policies [that] threaten to further restrict scientists’ ability to carry out research and communicate their findings.”

As directors of public research institutions, we uphold the idea that “Science is a process, not a product — a tool for discovery that allows us to constantly expand and refine our knowledge of the Universe.” We too face the problem of working with restricted budgets, and share the organizers’ conviction that “de-funding and hiring freezes in the sciences are against any country’s best interests.”

For these reasons, we fully support the initiative of this public-spirited march for the sciences.

Jean Chambaz, President of CURIF (Coordination of French Research-Intensive Universities)

Alain Fuchs, President of CNRS

Yves Lévy, CEO of INSERM

Philippe Mauguin, CEO of INRA

Antoine Petit, Managing Director of INRIA

Daniel Verwaerde, Chairman of the CEA


For further information:

In France, marches are scheduled in Paris, Lille, Lyon, Toulouse and Montpellier.

Epstein-Barr virus and cancer: new tricks from an old dog

image d’amplification de centrosomes induite par l’infection par le virus Epstein Barr

Almost everybody has it: Scientists estimate that approximately 95 percent of adults around the world are infected with the Epstein-Barr virus. In rare cases, an infection with this virus causes cancer. Scientists at the German Cancer Research Center (DKFZ), at the German Center for Infection Research (DZIF), and at the French National Institute of Health and Medical Research (Inserm) have now discovered that a component of the Epstein-Barr virus infectious particle promotes carcinogenesis. This viral protein interferes with cell division and impairs proper distribution of the genetic material to the two daughter cells. This confers a risk of subsequent cancer development.

After an infection with the Epstein-Barr virus (EBV), the virus persists in the body throughout a person’s lifetime, usually without causing any symptoms. About one third of infected teenagers and young adults nevertheless develop infectious mononucleosis, also known as glandular fever or kissing disease, which usually wears off after a few weeks. In rare cases, however, the virus causes cancer, particularly lymphomas and cancers of the stomach and of the nasopharynx.

Scientists have been trying for a long time to elucidate how the viruses reprogram cells into becoming cancer cells. “The contribution of the viral infection to cancer development in patients with a weakened immune system is well understood ” says Henri-Jacques Delecluse, a cancer researcher at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg. “But in the majority of cases, it remains unclear how an EBV infection leads to cancer development.”

In their present publication, Delecluse, in collaboration with Ingrid Hoffmann, also from the DKFZ, and their respective groups present a new and surprising explanation for this phenomenon. The scientists have shown for the first time that a protein component of the virus itself promotes the development of cancer. When a dividing cell comes in contact with Epstein-Barr viruses, a viral protein present in the infectious particle called BNRF1 frequently leads to the formation of an excessive number of spindle poles (centrosomes). As a result, the chromosomes are no longer divided equally and accurately between the two daughter cells – a known and acknowledged cancer risk factor. By contrast, Epstein-Barr viruses that had been made deficient of BNRF1 did not interfere with chromosome distribution to the daughter cells.

EBV, a member of the herpes virus family, infects B cells of the immune system. The viruses normally remain silent in a few infected cells, but occasionally they reactivate to produce viral offspring that infects nearby cells. As a consequence, these cells come in close contact with the harmful viral protein BNRF1, thus having a greater risk of transforming into cancer cells.

“The novelty of our work is that we have uncovered a component of the viral particle as a cancer driver,” Delecluse said. “All human tumors viruses that have been studied so far cause cancer in a completely different manner. Usually, the genetic material of the viruses needs to be permanently present in the infected cell, thus causing the activation of one or several viral genes that cause cancer development. However, these gene products are not present in the infectious particle itself”.

Delecluse and his colleagues therefore suspect that EBV could cause the development of additional tumors. These tumors might have previously not been linked to the virus because they do not carry the viral genetic material.

For Delecluse, the consequence that follows from his findings is immediate: “We must push forward with the development of a vaccine against EBV infection. This would be the most direct strategy to prevent an infection with the virus. Our latest results show that the first infection could already be a cancer risk and this fits with earlier work that showed an increase in the incidence of Hodgkin’s lymphoma in people who underwent an episode of infectious mononucleosis.”

Experts estimate that an EBV vaccine could prevent two percent of all cancer cases worldwide. Delecluse and his group already developed a vaccine prototype in 2005. It is based on so-called ‘virus-like particles’, or VLPs. These are empty virus shells that mimic an EBV infectious particle, thus prompting the body to mount an immune response. However, “Of course, the VLPs must not contain BNRF1!” Delecluse hastens to add.

Socioeconomic environment and incidence of cancer in France

Almost 15,000 cases of cancer could be prevented in France each year by improving living conditions and promoting health among the most vulnerable populations. These were the conclusions of a study published in the weekly epidemiological report Bulletin épidémiologique hebdomadaire (BEH), and coordinated by Inserm Unit 1086 “Cancer and Prevention” located in Caen.

A growing statistically significant incidence rate among socially deprived populations was observed for stomach cancer, liver cancer, cancer of the lips-mouth-pharynx, and lung cancer in both genders, as well as for laryngeal cancer, esophageal cancer, pancreatic cancer, and bladder cancer in males, and cervical cancer in females.

Read the entire BEH

4 February 2017: World Cancer Day

cancer cell


World Cancer Day, which will take place on 4 February next, will be an opportunity to make the general public aware about prevention, detection and treatment of this disease.

Inserm researchers remain committed to advancing research, on improving patient care as well as on the efficiency of existing therapies, and on improving the diagnosis of certain cancers. Here are a few recent examples.

Researchers from Inserm Unit 1121, “Biomaterials and Bioengineering” (Inserm/University of Strasbourg), have improved the artificial larynx that they developed 5 years ago, and have optimised their surgical technique. Thus a patient with cancer who had undergone a laryngectomy has been wearing this implant for the last 18 months, allowing him to breathe through his mouth and nose, and restoring his speech and sense of smell, thereby improving his daily life.

See the press release Un patient bénéficie d’un larynx artificiel depuis 18 mois” (A patient has benefited from an artificial larynx for 18 months), published on 17 January 2017. 

The members of the “Center for Infection and Immunity of Lille” (Inserm/CNRS/University of Lille/Institut Pasteur Lille), at Inserm Unit 1019, have identified the nature and mode of action of bacterial species capable of optimising the anti-tumour response induced by chemotherapy. They have thus demonstrated the essential role of the gut microbiota in the efficacy of chemotherapy.

See the press release “The gut microbiota to the rescue of chemotherapies,” published on 5 October 2016. 

In October 2016, Inserm inaugurated its first accelerator of technological research (ART). Based in Paris, the “biomedical ultrasound” ART is devoted to the research and use of ultrasound, particularly in the area of cancer diagnosis and treatments.

See the press release “Creation of first accelerators of technological research at Inserm,” published on 26 October 2016. 

Researchers from Paris Descartes University, the Paris Public Hospitals (AP-HP) and Inserm have developed a method that enables large-scale use of circulating tumour DNA in patients with lung and pancreatic cancer. Ultimately, this method will be widely used in the different Molecular Biology platforms, to improve the diagnosis of certain cancers and guide the prescription of treatments.

See the press release “Towards an improved diagnosis of certain cancers,” published on 28 September 2016.